Transcript Introduction to the Autonomic Nervous System

Introduction to the Autonomic
Nervous System
George Howell III, Ph.D
Nervous system hierarchy
Enteric
Nervous
System
Autonomic nervous system
• Independent – activities are not under direct
conscious control (autonomic = automatic)
• Divided into parasympathetic, sympathetic,
and sometimes ENS on an anatomical basis
• Parasympathetic vs sympathetic divisions
– Origin – IML vs CNS nuclei
– Ganglia – paravertebral and prevertebral vs
ganglia at target organ
– Primary neurotransmitters – Ach vs NE
Origination of the PNS
What’s missing??
Synapses of the PNS
Synaptic
transmission
1.
2.
3.
4.
5.
6.
7.
Synthesis of neurotransmitter
from precursors
Action potential spreading
depolarization
Activation of VGCa+ channels
Ca+ dependent fusion of
neurotransmitter containing
vesicles with plasma membrane
Release of transmitters into
cleft and binding to
postsynaptic receptors
Termination of transmitter
action via degradation or
reuptake in presynaptic
Activation of postsynaptic cell
Major neurotransmitters of the ANS
• Acetylcholine (Ach)
– Fibers using Ach are cholinergic fibers
– Almost all fibers leaving CNS are cholinergic
– Major transmitter of preganglionic fibers (sympathetic and
parasympathetic)
– Major transmitter of parasympathetic postganglionic synapse and Nm
junction
• Some parasympathetic postganglionics use peptides and NO as modulators
– Nicotinic and muscarinic receptors
• Norepinephrine (NE)
– Fibers using NE are adrenergic fibers
– Major transmitter at sympathetic postganglionic synapse
• Some sympathetic postganglionics use Ach
– Adrenergic receptors
• Alpha and beta
Other neurotransmitters of the ANS
• Dopamine
– Modulator in some ganglia and ENS
– Sympathetic transmitter in renal
blood vessels
• Serotonin
– Excitatory in ENS
• GABA
– Inhibitory
• Substance P
– Sensory neurotransmitter
– Excitatory with Ach at Nm junction,
vasodilator due to NO release,
nociception at peripheral nerve
synapses
• Vasoactive intestinal peptide
– Excitatory secretomotor transmitter
in ENS, vasodilator, cardiac
stimulant
• Adenosine triphosphate (ATP)
– Transmitter or cotransmitter at ANS
effector synapses
• Enkephalins and other endogenous
opioids
– Inhibitory effect on secretomotor
interneurons in ENS, inhibit peristalsis,
stimulate secretion
• Gastrin releasing peptide (GRP)
– Promotes gastrin release from G cells
in stomach
• Neuropeptide Y
• Nitric oxide (NO)
– Synthesized on demand by NOS…..not
stored
– Vasodilation
Cholinergic synapse
•
Synthesis of acetylcholine
–
–
Choline is taken up into presynaptic cell by
Na+ dependent choline transporter (rate
limiting step)
Acetyl CoA + choline = acetylcholine
•
–
Transported into vesicles by vesicle associated
transporter (VAT)
•
•
v-SNAREs (synaptobrevin; subgroup of
VAMPs) bind with t-SNAREs (SNAPs; syntaxin
and SNAP-25) to mediate vesicular fusion
•
•
Ca+ dependent
Blocked by botulinum toxin
Presynaptic and postsynaptic responses
to Ach (muscarinic and nicotinic
receptors)
–
•
Other cotransmitters are also stored in vesicle
Vesicular release
–
•
Catalyzed by choline acetyltransferase
Presynaptic receptors – auto and
heteroreceptors
Acetylcholinesterase mediated
degradation
–
–
Acetylcholine to choline + acetate
Terminates action of acetylcholine in cleft
Cholinergic receptor subtypes and actions
Nicotinic
• Ligand gated Na+
channels
• Directly mediate
depolarization in
excitable cells
• Two subtypes:
neuronal (Nn) and
muscular (Nm)
•
•
•
•
Muscarinic
GPCRs
5 subtypes
M1, 3, 5 are
coupled to Gq Gproteins
M2, 4 are coupled
to Gi G-proteins
Role of each cholinoceptor at autonomic ganglia
•
Nn – milliseconds
–
–
•
M2 – seconds
–
–
–
•
Inhibitory postsynaptic potential (IPSP)
Follows AP
Mediated by opening of K+ channels
M1 – seconds
–
–
•
Excitatory postsynaptic potential (EPSP)
Temporal or spacial summation leads to AP
Slow EPSP by closing K+ channels
Follows IPSP
Peptides – minutes
–
–
Late, slow EPSP
Modulates response of postsynaptic cell to subsequent inputs
Adrenergic
synapse
• Synthesis of NE
• Vesicular transport
• VMAT
• Dopamine converted
to NE in vesicle
• Neurotransmitter release
• Vesicular fusion similar
to that of the
cholinergic synapse
• Neurotransmitter actions
• Postsynaptic and
presynaptic receptors
• Transmitter reuptake
• NET and DAT terminate
neurotransmitter
action
Adrenergic receptor subtypes and actions
Alpha
• GPCRs
• Two subtypes
• A1 – Gq protein
coupled
• A2 – Gi protein
coupled
Beta
• GPCRs
• Three subtypes
• B1-3 – Gs
protein coupled
Autonomic regulation of organ
systems
Baroreceptor reflex
• Increase in MAP
• Increased
baroreceptor
firing
• Increase
parasympath
etic tone
• Decrease
sympathatic
tone
• Decrease in MAP
• Decreased
baroreceptor
firing
• Decrease
parasympath
etic tone
• Increase
sympathetic
tone
Autonomic regulation of
cardiovascular function
Enteric Nervous System
• Large and highly organized system of neurons located
in the walls of the gastrointestinal system
• It is often considered a third division of the
autonomic nervous system
• Includes the myenteric plexus (of Auerbach) and the
submucous plexus (of Meissner)
Enteric nervous system
Parasympathetic
Longitudinal muscle
Myenteric plexus
Circular muscle layer
Submucosal plexus
• Walls constricted
and sphincters
relaxed via M3
• Secretions
increased via M3
Autonomic regulation of structures
associated with the eye
Dominant tone = Parasympathetic
Iris radial – contracted
via alpha-1
Iris circular –
contracted via M3
Ciliary muscle –
contracted via M3
Regulation of the heart
Dominant tone = parasympathetic
Sympathetic
Increases heart rate
and contractility via
beta-1 and 2
(primarily beta-1)
Parasympathetic
Decreases heart
rate and atrial
contractility via M2
Regulation of the blood vessels
Veins
Arterioles/arteries
Dominant tone =
parasympathetic
Dominant tone =
sympathetic
Contraction via
alpha1
Relaxation via
beta-2
Regulation of the liver
• Sympathetic
– Increase gluconeogenesis and glycogenolysis
– Provide glucose to fuel “flight or fight” response
– Primarily beta-2, possibly alpha-1
Control of stomach acid
Parasympathetic
• Increase histamine
release from ECL cell
via M3
• Increase H+
production from
parietal cell in
fundus via M3
• Decrease
somatostatin release
from D cell in
antrum
• Increases
gastrin release
from G cell
Regulation of the bladder
Parasympathetic
• Bladder wall
– Constriction via M3
– Relaxation via beta-2
• Sphincter
– Relaxation via M3
– Constriction via
alpha-1
Glandular secretion
Sweat
Salivary
Increased via M3
Appocrine – increased via
alpha-1
Eccrine – increased via M
Lacrimal gland (tear production) – increased via M
Predominant tones of major organ
systems
•
•
•
•
•
•
•
•
•
•
•
Heart - parasympathetic
Arterioles/arteries - sympathetic
Veins - sympathetic
Iris - parasympathetic
Ciliary muscle - parasympathetic
GI tract (ENS) - parasympathetic
Smooth muscle - parasympathetic
Bladder - parasympathetic
Sweat glands - sympathetic
Salivary glands – parasympathetic
Lacrimal glands – parasympathetic
Physiological effects of autonomic innervation and
receptors that govern the effect
Parasympathetic
• Contracts the ciliary muscle
via M-3
• Decelerates the sinoatrial
node via M-2
• Decreases heart contractility
via M-2
• Releases EDRF in the
endothelium via M-3, M-5
• Contracts bronchiolar
smooth muscle via M-3
• Contracts GI walls via M-3
• Relaxes GI sphincters via M-3
• Increases GI secretions via
M-3
• Contracts the uterus via M-3
• Causes erection of the penis
via M
Sympathetic
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Contracts the iris radial muscle via alpha-1
Relaxes the ciliary muscle via beta
Accelerates the sinoatrial node via beta-1,2
Accelerates ectopic pacemakers via beta-1,2
Increases cardiac contractility via beta-1,2
Relaxes bronchiolar smooth muscle via beta-2
Relaxes GI walls via alpha-2, beta-2
Contracts GI sphincters via alpha-1
Relaxes bladder wall via beta-2
Contracts bladder sphincter via alpha-1
Contracts uterus via alpha, relaxes uterus via
beta-2
Contracts pilomotor smooth muscle via alpha
Activates sweat glands via alpha, M
Increases gluconeogenesis and glycogenolysis
in liver via beta-2 and alpha
Induces lipolysis via beta-2
Increases renin release from kidney via beta-1