Nerve and Muscle

Physiology of nerve

The neuron

• The basic structural unit of the nervous system.

• Structure: • The soma • The dendrites: antenna like processes • The axon: hillock, terminal buttons

Types of nerve fibers

a- myelinated nerve fiber:

• Covered by

myelin sheath

, protein-lipid layer, secreted by

Schwann cells

, acts as

insulator

to ion flow, interrupted at

Nodes of Ranvier

b- unmyelinated nerve fiber:

• Less than 1μ, covered only with Schwann cells, as postganglionic fibers

Electrical properties of a neuron

• Electrical properties of nerve & muscle are: • 1-There is difference in

electrical potential

between the inside and outside the membrane • 2-

Excitability

: the ability to respond to any stimulus by generating action potential • 3-

Conductivity

: the ability to propagate action potential from point of generation to resting point

•

Membrane potential

; the basis of excitability

Def:

electrical difference between the inside & outside the cell • •

Causes

:

selective permeability

of the membrane more K+, Mg2+, Ptn, PO4 inside • • • • Exists in all living cells & it is the basis of excitability

Excitability:

Def:

more Na+, Cl-, HCO3-outside it is the ability to respond to stimuli (change in the environment) giving a response • • The most excitable tissues are nerves & muscles • Stimuli: +anode - cathode

Types:

• Electrical (preferred), chemical, mechanical, or thermal.

• Cathode ( more important) & anode

Excitability

• • Factors affecting effectiveness of the stimulus:

1- strength

: • effective stimulus •

2- duration:

• a certain period of time, very short duration can not excite the nerve •

3- rate of rise of stimulus intensity:

• Rapid increase…. Active response • Slow increase …. adaptation

Strength –Duration Curve

• • •

Within limits stronger intensity shorter duration Strength:

• • •

Subthreshold stimulus

: causes local response (electrotonic) •

Duration:

• stimuli of very short duration can not excite the nerve

Utilization time

: is

the time

needed by

(Rheobase)

to give a response

threshold

stimulus

:

Threshold stimulus (rheobase):

it is the minimal amplitude of stimulus that can excite the nerve and produce action potential.

Chronaxie

time

needed by a stimulus

double the rheobase

to excite the nerve, it is a

measure of excitability

, decrease chronaxie means increase excitability

Strength –Duration Curve

chronaxi e

2R

Utilization time

duration R

Measuring the membrane potential

Recording

: by 2 micoelectrodes inserting one inside the fiber & the other on the surface & connected to a voltmeter through an amplifier

Types of membrane potential

• • Membrane potential has many forms:

1- RMP

• 2- on stimulation; • a)

action potential

if threshold stimulus • b)

localized response

(

electrotonic

) if subthreshold stimulus

Resting membrane potential (RMP)

*

definition:

It is the

difference

in

electrical potential

between the inside and outside the

cell membrane

under

resting

conditions with the inside negative to the outside

Recording

: by 2 micoelectrodes inserting one inside the fiber & the other on the surface & connected to a voltmeter •

Value:-90 mv large fibers, -70 in medium fibers, -20 in RBCs

•

Causes

• 1- selective permeability • 2- Na-K pump

Resting Membrane Potential

    Selective permeability of the membrane: contributes to -86mv  K+, ptn-, Mg2+&PO4- are concentrated inside the cell    Na+, Cl-, HCO3- are found in the extracellular fluid During rest the membrane is 100 times more permeable to K+ than to Na+, K+tend to move outward through

INWARD RECTFIER K+

channels down their concentration gradient The membrane is impermeable to intracellular Ptn-&other organic ions Accumulation of

+

ve charges outside & -ve charges in At equilibrium :K+ in to out is 35:1 Na+ in to out is 1-10

Potassium equilibrium

-90 mV

Na-K pump

• Definition: carrier protein on the cell membrane: • 3 binding sites inside for Na+ • 2 sites outside for K+ • 1 site for ATP • Inner part has ATPase activity • It is an electrogenic pump Contributes for -4mv and helps to keep RMP

•

Nernest equation

• E for K = -61 log con inside/ conc outside =- 94 • E for Na = -61 log con inside/ conc outside =+ 61 •

Goldman equation

: it considers • 1- Na, K and cl concentrations.

• 2- K permeability is 100 times as that for Na

Action Potential

• Definition: It is the rapid change in membrane potential following stimulation of the nerve by a threshold stimulus.

• Recording: microelectrodes and oscilloscope.

Membrane Permeabilites

• •

AP is produced by an increase in Na + permeability.

After short delay, increase in K + permeability.

Figure 7-14

Shape and Phases of Action Potential

• 1- Stimulus artifact.: small deflection indicates the time of application of stimulus, it is due to leakage of current • 2- Latent Period: isoelectrical interval, time for AP to travel from site of stimulation to recording electrode.

• 3- Ascending limb (depolarization):starts slowly from -90, till firing level-65mv, reaches &overshoots the isopotential, ends at +35 • 4- Descending limb:(repolarization): starts rapidly till 70% complete then slows down * Hyperpolarization: in the opposite direction • slight & prolonged 5- RMP

Shape and Phases of Action Potential

1- Ascending limb (depolarization) Slow..firing level..rapid.

2- Descending limb (repolarization) rapid then slow 3- Hyperpolarization: slight & prolonged 4- RMP +35 0 -65 -90 FL Latent period overshoot depolarization repolarization hyperpolarization time

Duration of Action Potential

• Spike lasts 2msec • Hyperpolarization 35-40msec

Ionic basis of action potential

• •

Depolarization is caused by Na+ inflow Repolarization is caused by K+ outflow

Two types of gates: 1-

voltage gated Na+ channels

; having 2 gates: outer activation gate & inner inactivation gate 2-

voltage gated K+ channels

; one activation gate When the nerve is stimulated:: a- the

outer gate

of VG Na+ opens,

activating Na+ channel

…. Na+ inflow b- the

inner gate

of Na+ channels closes,

inactivating Na+ channels

… stop Na inflow c-

K+ gates open

,

activating K+ channels

, K+ outflow

The Action Potential A stimulus opens activation gate Na + channels of some depolarizing membrane potential, allowing some Na to enter, causing further depolariztion If threshold potential is reached, all Na + channels open, triggering an action potential.

The Action Potential

1-Depolariztaion:

occurs in 2 stages:

Slow stage

: -90 to -65mv: some Na + channels opened, depolarizing membrane potential, allowing some Na to enter, causing further depolarization At

-65mv

, the

firing level

or threshold for stimulation, all Na + channels open, triggering an action potential.

Rapid stage

: -65 to +35: all Na+ channels are opened, Na+ rush into the fiber, causing rapid depolarization

The Action Potential Within a fraction of msec, Na + channel inactivation gates close and remained in the closed state for few milliseconds, before returning to the resting state.

2- Repolarization:

Inactivation of Na+ channels and activation of K + channels are fully open.

Efflux of K + from the cell drops membrane potential back to and below resting potential

3- Hyperpolarization;

slow closure of K+ channels

The Action Potential

The Na+ & K+ gradients

after action potential

are re-established by

Na+/K+ pump

Only very minute fraction of Na+ & K+ share in action potential from the total concentration The action potential is

an all-or-none response.

(provided that all conditions are constant, AP once produced, is of maximum amplitude, constant duration & form, regardless the amplitude of the stimulus , however threshold or above Action potential will not occur unless depolarization reaches the FL (none ) Action potential size is independent of the stimulus and once depolarization reaches FL, maximum response is produced, reaches a value of about +35 mV(all)

The Action Potential Both gates of Na + channel are closed but K + channels are still open.

K + channels finally close and Na + channel inactivation gates open to return to resting state.

Continued efflux of K + keeps potential below resting level.

Action potential initiation

S.I.Z.

Action potential termination

Action potential in a nerve trunk

• Nerve trunk is made of many nerve fibers • The AP recorded is compound action potential, having many peaks • The individual fibers vary in: • 1- threshold of stimulation • 2-distance from stimulating electrode • 3- speed of conduction

• During depolarization, there is +ve feed back response.

• Repolarization is due to: 1- inactivation of Na+ channels( must be removed before another AP 2- slower & more prolonged activation of K+ channels • Hyperpolarization (undershoot): slow closing of K+ channels, K+ conductance is more than in resting states • Role of Inward rectifier K+ channels: Non gated channels Tend to drive the membrane to the RMP Drive K+ inwards only in hyperpolarization Re-establishing Na+ &K+ gradient after AP:role of Na+ /K+ pump All or none law

• Electrotonic potentials & local response

Catelectronus:

at cathode/ depolarization less than 7mV/ passive •

Anelectronus

: at anode/ hyperpolarization/ passive •

Local response (local excitatory state):

• Stonger cathodal stimuli • Slight active response • Some Na+ channels open, not enough to reach FL • It is graded • Does not obey all or none law • Non propagated • Excitability of the nerve increased • Caused by subthreshold stimulus • Can be summated & produce AP • Has no refractory period

Local Response (local excitatory change)

• Although

subthreshold

stimuli do not produce AP they produce slight

active changes

in the membrane that

DO NOT PROPAGATE.

• It is a state of slight depolarization caused by subthreshold

cathodal

stimulus that opens

a few Na channels not enough

to produce AP

Local Response (local excitatory change)

• It differs from AP : • It does not obey all or non rule • Can be graded.

• Can be summated.

• It does not propagate.

Excitability changes during the action potential •

Up to FL, excitability increases

The remaining part of action potential, the nerve is refractory to stimulation (difficult to

•

be restimulated)

Absolute refractory period: Def

: the period during which a 2 of the stimulus nd AP can not be produced whatever the strength

Length:

from FL to early part of repolarization •

Causes:

inactivation of Na+ channels

Relative refractory period: Def.;

the period during which membrane can produce another action potential, but requires stronger stimulus.

Length:

from after the ARP to the end of the AP

Causes:

some Na+ channels are still inactivated K + channels are wide open.

FL

ARP I ncreased excitability RRP

Factors affecting Membane potential & Excitability • Factors ↑ excitability: • *

Role of Na+

• 1) ↑ Na permeability (veratrine & low Ca 2 +).

• Factors ↓ excitability: • 1)↓ Na permeability( local anaesthesia & high Ca2+) [ membrane stbilizers] • Decrease Na+ in ECF: decreases size of AP, not affecting RMP • Blockade of Na+ channels by tetradotoxin TTX decrease excitability & no AP •

** Role of K+:

• 1)↑ K extracellularly (hyperkalemia).

• 2)↓ K extracellularly (hypokalemia): familial periodic paralysis • • 3) blockade of K+ channels by TEA: prolonged repolarization& absent hyperpolarization

*** Role of Na+ K+ pump

AP : only prolonged blockade can affect RMP &

Accommodation of nerve fiber

• Slow increase in the stimulus intensity gives no response: • 1- inactivation of Na+ Channels • 2- opening of K+ Channels

Conduction in an Unmyelinated Axon

• • • •

The action potential generated at one site, acts as a stimulus on the adjacent regions During reversal of polarity, the stimulated area acts as a current sink for the adjacent area A local circuit of current flow occurs between depolarized segment & resting segments (flow of +ve charges) in a complete loop of current flow The adjacent segments become depolarized, FL is reached, AP is generated Figure 7-18

Conduction in Myelinated Axon

(Saltatory conduction)

• Myelin prevents movement of Na + and K + through the membrane.

• The conduction is the same in unmyelinated nerve fibers Except that

AP is generated only at Nodes of Ranvier

• AP occurs only at the nodes.

– AP at 1 node depolarizes membrane to reach threshold at next node.

• The +ve charges

jump

from resting Node to the the neighbouring activated one

(Saltatory conduction).

Figure 7-19

Importance of saltatory conduction:

• ↑ velocity of nerve conduction.

• Conserve energy for the axon.

Orthodromic & antidromic conduction

• Orthodromic: from axon to its termination • Antidromic: in the opposite direction • Any antidromic impulse produced, it fails to pass the 1 st synapse & die out

Monophasic &biphasic AP

• Monophasic AP: recorded by one microelectrode inserted inside the fiber & one indifferent microelectrode on the surface.

• Biphasic: two recording electrodes on the outer connected to CRO

Depolarization & repolarization of a nerve fiber • RMP does not record any change • Depolarization flows to the +ve electrode ..... Upright deflection (+ve wave) • Complete depolarization ... No flow of current (baseline) • Repolarization to the +ve electrode....down deflection • Complete repolarization ... No flow of current (baseline)

Action potential in a nerve trunk

• Nerve trunk is made of many nerve fibers • The AP recorded is compound action potential, having many peaks • The individual fibers vary in: • 1- threshold of stimulation • 2-distance from stimulating electrode • 3- speed of conduction

Compound AP

• Graded • Subthreshold; no response occurs • Threshold; a small AP, few nerve fibers • Further increasing; AP amplitude increases up to a maximal • Increasing the intensity, supramaximal stimuli, no more increase in the AP

Nerve fiber types

• According to their thickness, they are divided into: A fibers B fibers C fibers

diameter

2-20 micron

conduction

20-120m/s

Spike duration

0.5 msec

Remarks

Alpha, beta, gamma & delta Most sensitive to pressure 1-5 micron 5-15m/s 1msec <1 micron 0.5-2m/s 2msec Preganglionic autonomic f Most sensitive to hypoxia Postganglionic autonomic f Most sensitive to local anesthetics

• • • • • • • • •

Metabolism of the nerve

Rest

: nerve needs energy to maintain

polarization

of the membrane, energy needed for Na+/K+ pump, derived from ATP.

Resting heat

Activity

:

pump

activity increases to the

3 rd power of Na+ concentration inside

, if Na+ concentration is doubled, the pump activity increases 8 folds;2 3 .

Heat production increases

: 1 initial heat during AP 2 a recovery heat, follows activity =30 times the initial heat

Neurotrophins: Proteins necessary for neuronal development, growth & survival Secreted by glial cells, muscles or other structures that neuron innervate Internalised & retrograde transported to the cell body

Types of muscles

• Skeletal muscle: under voluntary control 40% of total body mass.

• Cardiac muscle: not under voluntary control.

• Smooth muscle: not under voluntary control. Both are 10% of total body mass

Skeletal muscles

• Attached to bones • >400 voluntary skeletal muscles • • Contraction depends on their nerve supply

4 functions:

• 1- force for locomotion & breathing • 2- force for maintaining posture & stabilizing joints • 3- heat production • 4- help venous return

Morphology

•

Muscle fibers:

• Bundled together by

C.T

.

• Arranged

in parallel

between 2 tendenious ends • Is a single cell • Closely enveloped by glycoprotein sheath (

sarcolemma

) outside the cell membrane • Made of many parallel

myofibrils

embeded in a sarcoplasm, between a complex

tubular system

Skeletal muscle

• • • • Each

muscle fiber

parallel

myofibrils

is a single unit. It is made up of many embedded together and a complex

sarcotubular system

. • • Each muscle fibril contains interdigitating

thick and thin myofilaments

arranged in

sarcomeres.

2 major proteins: 1- thick filaments [myosin] 2- thin filaments [actin, troponin, troopomyosin]

Troponin & trpomyosin regulate muscle contraction by controlling the interaction of actin & myosin

• • • • • muscle.

sheets called

The sarcomere

• It is the functional unit of the • It ext\ends between two

Z lines.

Thick filaments (Myosin) in the middle (dark band (A)).

Thin filaments on both sides (light band (I) ).

Z line in the middle of I band. H zone in the middle of A band.

When the muscle is stretched or shortened, the thick & thin filaments slide past each other, and the I band increases or decreases in size

Internal organization:

Striations:

• • • • • • • • • •

Myofilaments

1- thick filaments (myosin):

300 myosin molecules 2 heavy chains & 4 light chains Each myosin molecule has

two heads

attached to a double chains forming

helix tail.

myosin head contain

actin – binding

site, an

ATP- binding

site and a catalytic site (

ATPase

). Each myosin head protrude out of the thick filaments forming

cross bridges

that can make contact with the actin molecule

2- Thin filaments (actin) Actin, tropomyosin, troponin.

Actin sites

is a double helix that has

active

for combines with myosin cross bridges.

Troponin:

3 subunits I for Actin binding, T for tropomyosin binding, C for Ca binding.

Sarcotubular system

• • • • • • • • • Consists of

T-tubules T tubules

and

Sarcoplasmic reticulum.

consists of network of transverse tubules surround each myofibril, at the junction of the dark and light bands.

T tubules T tubules T tubules

are invaginations from cell membrane.

contain extracellular fluid.r

transmit the AP from the surface to the depth of the muscle fiber.

Sarcoplasmic reticulum Sarcoplasmic reticulum Sarcoplasmic reticulum Sarcoplasmic reticulum

: surrounds each myofibril, run parallel to it : extends between the T tubules.

: are the sites for

Ca storage.

ends expands to form

terminal cistern,

which makes specialized contact with the T tubules on either side •

Foot processes

span the 200 A 0 between the 2 tubules • SR contains protein receptor called

Ryanodine

foot process and Ca channel that contains the • T tubule contains voltage- senstive opens the ryanodine channel

dihydropyridine

receptor that

The muscle protein

• Myosin protein: • Thick filaments: 300 myosin molecules • Myosin molecule is made up of 2 heavy chains coil around each other to form a helix.

• Part of the heliix extends to side to form an arm • Terminal part of the helix with 4 light chains combine to form 2 globular heads • The arm & head are called cross bridges, flexible at 2 hinges, one at the junction between the arm leaves the body, the 2 nd at the attachment of the head with the arm • The myosin heads contain an actin –binding site, catalytic site for hydrolysis of ATP

Myosin thick filaments

Thin filaments

Backbone is formed of 2 chains of actin, forming helix, has active site, 300-400 molecules Tropomyosin: long filaments, located in the groove between the 2 chains of actin, covers the active sites, 40-60 molecules.

Troponin: small, globular, formed of 3 parts; 1-TI 2-TT 3- TC Actin tropomyosin Ca2+

• α actinin binds actin to the Z line

Neuromuscular Junction •

Def

: it is the area lies between the nerve ending of the alpha motor neurons and skeletal muscle.

•

Structure of the NMJ :

•1) terminal knobs 2)Motor End Plate (MEP) 3)Synaptic cleft •contain Ach vesicle contain Ach receptors contain choline estrase •

Steps Of Neuromuscular Transmission

: •1) Arrival of action potential : ↑ permeability to Ca2+ .. Rupture of vesicles.

•2) Postsynaptic response : ↑ conductance to Na and K more Na influx…end plate potential •3) EPP : graded, non propagated response that act as a stimulus that depolarizes the adjacent membrane to firing level … AP…. Muscle contraction.

•4) Acetyl choline degradation

end plate

Neuromuscular junction

• Properties of neuromuscular transmission: • 1) unidirectional: from nerve to muscle • 2) delay: 0.5msec • 3) fatigue: exhaustion of Ach vesicles.

• 4) Effect of ions: ↑ Ca….. ↑ release of Ach • • 5) Effect of drugs: * * ↑ Mg….↓ release of Ach

Drugs stimulate NMJ

• Ach like action Metacholine, carbachol, nicotine small dose.

• inactivating choline esterase neostigmine, physostigmine, diisopropyl phlorophosphate.

Drugs block NMJ

: curare competes with Ach for its receptors

Motor end plate is a highly specialized region of the muscle plasma membrane.

Myasthenia Gravis (MG)

      Serious may be fatal disease of

neuromuscular junction

Characterized by

weakness of skeletal muscle, easy fatigability

may affect the respiratory muscles and cause death More in female It is suspected to be a type of

autoimmunity

(the patient antibodies attack the acetyl choline receptors at the neuromuscular junction) Treatment: Adminestration of drugs as neostigmine, inactivating acetylcholinesterase

Changes that occurs in the skeletal muscle after its stimulation

1- electrical changes: action potential 2- Excitability changes: ends before the beginning of contraction 3- chemical changes: at rest & during activity 4- mechanical changes: contraction

Electrical changes

Nerve action potential Muscle action potential

RMP Rate of conduction duration After AP -70mV According to myelination -90mV 5m/sec shorter longer Release of acetyl choline Contraction after 2msec +35 +35 -70 -90

Excitability changes

• It is like changes that occurs in the nerve during

action potential

(increased excitability, ARP, RRP, Supernormal excitability, subnormal excitability, normal) • The refractory period ends during the latent period before the beginning of contraction, so during contraction, the excitability is normal, can respond to another stimuli Mechanical changes AP

Metabolic (Chemical) changes

At rest

: continuous metabolic activity to produce energy needed for: 1-maintenance of the polarized state (

RMP

) 2-

synthesis of ptn, glycogen

, other organic compounds 3- production of

muscle tone During activity

: energy consumption is markedly increased Converts chemical energy into mechanical energy The chemical energy is derived from: ATP, CP, glycogen, glucose The chief reactions are: 1- anaerobic breakdown of

ATP myosin

ADP+P+ E(12000 Cal) 2- ATP resynthesis by creatine phosphate, glycogen lactate & aerobic system ADP+

CP

→ creatine+ ATP (restored by reverse reaction during relaxation) Glucose +2ATP ( gycogen+ 1ATP) 2 lactic acid +4ATP Glucose +2ATP ( gycogen+ 1ATP) oxygen 6CO2+ 6H2O+ 40ATP Free fatty acids oxygen CO2+ H2O+ATP

• ATP is the only immediate energy of the muscle.

• ATP inside the muscle is enough only for 5-6 sec of maximal exercise • The muscle contains phosphocreatine 2-3 times as ATP • Phosphocreatine energy is transferred too ATP within a small fraction of a second • Phosphagen system: is ATP & CP is enough for max exercise for 10-15 sec (100m run) • Glycogen lactic acid system provide addition of 30-40 sec of max. exercise • Lactic acid produced from this system produces muscle fatigue, removal needs an hour or more by: • Lactic acid O2 pyrovic acid • Lactic acid is transformed to glucose inside the liver • Lactic acid may be used as a fuel by heart muscle

During recovery (oxygen debt)

• After exercise, rate of ventilation remains high to: • 1- remove lactate • 2- rebuilding of ATP& CP stores • 3- replace O2 taken from myoglobin • The extra post exercise O2 is called Oxygen dept • Measured by subtracting basal level from O2 consumption after exercise until basal consumption is reached

Motor unit:

Def: it is a single motor neuron , its axon, and the group of muscle fibres supplied by this axon In muscles perform fine movements, number of fibres in each motor unit is small In musclles perform gross movements, the number of fibres in each motor unit is large

Motor Unit

Mechanical changes [excitation-contraction coupling]

Action potential produce muscle contraction in 4 steps; • 1-

release of Ca2

+: AP pass through T tubules, causing Ca release from the terminal cistern into the cytoplasm • 2-

activation of muscle proteins:

Ca2+ binds troponin, moves tropomyosin away from active site of actin,

actin binds with myosin ,

contraction starts • 3-

generation of tension : binding, bending, detachment, return

• 4-

relaxation:

active process,

when Ca is removed frrom the cytoplasm &

actively pumped into the SR

Action Potentials and Muscle Contraction

Mechanism of muscle contraction

Cross-bridge formation:

Muscle Twitch

a single action potential causes a brief contraction followed by relaxation The twitch starts 2msec after the start of depolarization, before the repolarization is complete obeys all or none law All or none law: a single muscle fiber; either contracts maximally or does not contract at all under the same conditions

Types of Muscle Contractions

• Isotonic : Change in length (muscle shortens) but tension constant • Isometric : No change in length but tension increases e.g. Postural muscles of body • Muscle contraction in the body is a mixture of both types e.g. when person lifts a heavy object, the biceps starts isometric, then isotonic contraction

Isotonic and isometric contraction

CE SEC Isotonic contraction isometric contraction Rest contraction rest contraction

Muscle contraction

Types of contractions

:

1- isotonic contraction

: a- muscle shortens & tension constant b- sliding occurs c- mechanical efficiency :20% of (energy converted to work) & rest is lost as heat d- inertia & momentum that interferes with the recording of the twitch, so it lasts longer & needs more energy e- e.g. Moving a part of the body or the body as a whole

2- isometric contraction

: a- length of muscle is constant, the tension increases b- no much sliding c-no work is done (mechanical efficiency is zero) most energy is lost as heat d- e.g. Maintaining the posture against gravity

• • • Factors affecting muscle contraction

1- type of muscle fiber:

Slow Red fiber: Type I:

Small m.f., Slow nerve, Slow contraction & relaxation, not easily fatigued, low ATPase activity, large numbers of oxidative enzymes, large numbers of Capillaries , rich in Myoglobin , adapted for prolonged weight bearing, e.g. soleus muscle

Rapid pale fiber: Type IIb:

Larger fibers, Rapid neurons, Rapid contraction & relaxation, easily fatigued, extensive SR, Large amount of glycolytic enzymes, high ATPase activity , less capillaries, less myoglobin, less mitochondria, adapted for skilled movements, e.g. hands & extraocular muscles

• •

2- stimulus factor

:

Stimulus strength

: the more strength of the stimulus, the more the fibers stimulated, the more force of contraction (maximal stimulus) •

Stimulus frequency:Treppe (stair case phenomenon)

• low frequency; separate twitches • Medium frequency; clonus • High frequency; tetanus

Treppe

• Graded response • Occurs in muscle • Each subsequent contraction is stronger than previous until all equal after few stimuli

• •

3- type of load:

Preload:

load applied to the muscle before contraction changing its initial length, [within limits, the more the initial length, the more the tension in isometric contraction] •

Afterload

: load added to the muscle after it starts contraction [the more the after load, the less will be the velocity of contraction

LENGTH-TENSION CURVE TOTAL TENSION ACTIVE TENSION TENSION EQUILIBRIUM LENGTH LENGTH LENGTH PASSIVE TENSION OPTIMAL LENGTH (L o ) RESTING LENGTH

Muscle Length and Tension

TENSION SARCOMERE LENGTH (



)

Load velocity curve Vmax 10 5 P0 0 5 Load (gm) 10 ↑ afterload → ↓velocity of shortening (dl/dt) ,

•

4- fatigue:

repeated stimulation of the muscle results in fatigue due to: • Depletion of

ATP

,CP & glycogen consumption of

acetyl choline

• Accumulation of

metabolites

decreased

O2 & nutrient supply

Length –Tension curve

•

Passive tension

: is the tension in the muscle when passively stretched •

Active tension

: is the tension in the muscle generated by its contraction •

Total tension

: is the sum of the 2 • Maximal tension is obtained when the sarcomere length is 2.2μ; optimal overlap between myosin & actin • Increasing the length, decreases the force; some cross bridges do not have actin molecules to bind with • Dereasing the length, decreases the force; the ends of actin filaments overlapping each other & more difficult for the muscle to develop force

Load velocity curve

•

Increasing the afterload:

1- the velocity of shortening decreases; as each cross bridge cycle takes more time 2- the amount of shortening decreases; the ability to generate force decreases 3-V max occurs when the afterload is 0 (theoritically) • Muscles with more fast fibers have greater V max

Electromyography

• Is a record of electrical activity of the muscle using a cathode ray oscilloscope, picking up the electrical activity by metal dic electrode placed on the skin over the muscle or by hypodermic electrode inserted in the muscle • The record is called electrograph

Grading of the muscular activity

• There is little activity in the muscle at rest: • A- with

minimal

voluntary activity,

a few motor units

discharge, with

increasing

voluntary effort,

more units

contract • B- the force of voluntary movement is also increased by increasing

the frequency

of discharge, leading to tetanic contractions • Moderate intensity of rate of discharge contraction of the whole muscle → clonic contractions. The motor units contract asynchronously, the responses fuse into smooth

•

Muscular hypertrophy:

• Increase in size as a result of forceful muscular activity. The muscle fiber increase in thickness , increase in number of myofibrils and content of ATP, CP, glycogen. No increase in the number of the fibers .

Reaction of muscle to denervation

• If the nerve supply of the muscle is injured, the muscle is paralyzed (LMNL) • a-

the muscle atrophies

: decrease in size & the fibers are replaced by fibrous tissue • • b-

muscle fasciculation

: the nerve fibers degenerate spontaneous impulses are discharged in the 1 st few days, contractions seen on the surface of the skin , can be picked up by surface electrode EMG • c-

muscle fibrillation

: after all the nerve es to the muscle are damaged, spontaneous impulses start to appear in the muscle fibers, resulting in very weak contractions, cannot be seen, can be recorded by needle electrode EMG. Caused by increased sensitivity to circulating Ach ( denervation hypersensitivty )

d- reactioon of degeneration

Rigor mortis

• Contracture, rigid without action potentials • Several hours after death • Caused by loss of ATP, needed for relaxation • Ends when the muscle proteins are destroyed by bacterial action 15-25 hrs later.

• Has medicolegal importance

Smooth muscle

• Involuntary, supplied by autonomic nervous system •

Types: Single unit (visceral) Smooth muscle

: • Sheats of mfs, membranes become adherent to each other at multiple points, many gap junctions, contract in a coordinated manner

Multiunit smooth muscle

: fine movement as in ciliary m, iris of the eye, every fiber contracts independently

Characters:

1- thinner than cardiac muscle fibers 2- no striations, no sarcomere, no Z line (dense bodies), no troponin (calmodulin) 3- sarcoplasmic reticulum are absent

Membrane potential & action potentials

• Unstable membrane • Relative RMP is -50mV • Waves of depolarization & repolarization • When depolarization reach -35mV, an action potential is produced • •

AP of smooth muscles are of 2 types:

Spike potentials

: similar to Sk m Ap on top of slow waves, or rhythmically (pace maker P), duration 50ms

AP with plateau

: similar onset, delayed repolarization for several hundreds or thousands milliseconds. The plateau accounts for prolonged periods of contraction

Role of Ca2+ channels • Cell membrane contains mainly VG Ca2+channels instead of Na+ • So depolarization occurs by inflow of Ca2+ not Na+, slow depolarization.

Contractile process of smooth muscle EC coupling

• Smooth m contains calmodulin instead of troponin • ↑Ca2+ in the cytoplasm binds to calmodulin • Ca2+/calmmodulin complex activates MLCK which phosphorylates regulatortory light chain on the head of myosin→hydrolysis of ATP and starts cycling & continue cycling until MLC phosphatase becomes active and dephosphorylates the cross bridges • Relaxation occurs by ↓ Ca2+ …MLCK inactivated… phosphatase removes phosphate from MLC …. Cycling stops

Mechanical properties

• Slower • Latch bridges • Ca2+ enters the cells by: Neurotransmitter (receptor activated Ca2+ channel) Voltage gated Ca2+ channels Release from SR through IP3 receptor • Ca2+ is determined by influx &release and rate of into SR or to outside the cell

Characteristics of contraction of smooth muscles 1-

spontaneous

contractions 2- initiated

by AP or without AP

by: • •

stretch Local factors: K+ / Alkalies … contracts Acids/ CO2/ ↓O2… relaxes Cold contracts Hormonal

3-Role of

nerve supply

: modifies 4-

Plasticity

5-

Fatigue resistant