Transcript excitable membranes

excitable
membranes
resting membrane potential
Basic Neuroscience NBL 120 (2007)
overview
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electrical signaling
dendritic synaptic inputs
transfer to the soma
generate APs
axonal propagation
 ionic basis of RMP
 passive membrane properties
 AP initiation & propagation
resting membrane potential
electrochemical gradients
equilibrium potentials - Nernst equation
driving forces – Ohm’s Law
GHK equation
what does the membrane do?
separate and maintain (pumps)
gradients of solutions with different
concentrations of charged ions
selectively allow certain ionic species to
cross the membrane
hence…..
measurement
+
-
0 mV
DS Weiss
measurement
+
-
0 mV
-70 mV
DS Weiss
resting membrane potential
 what is it?
 electrical potential difference between the inside
and outside of the cell
 why does it exist?
 differences in the concentrations of charged ions
inside and outside the cell
 selective permeability of the membrane to certain
ions
 active pumping of ions across the membrane
diffusion
Einstein
Brownian motion (diffusion)
random-walk
ions appear to move down their
concentration gradients
very fast over short distances
 for small molecules / ions ≈ 1 m in 1 ms
how to create a RMP
 electrochemical Na-K exchanger (& others)
 pumps ions against their concentration gradients
 2K ions in and 3Na ions out
 net negativity to the RMP
 requires energy (ATP)
 not generally required for maintaining the RMP in the
absence of activity, but necessary for setting up initial
conditions by creating concentration gradients
 initial conditions:
different distribution
of a K-salt
membrane is only
permeable to K
there is no potential
difference across the
membrane
 at equilibrium:
K ions diffuse down
concentration gradient
anions are left
behind: net negativity
develops inside the cell
further movement of
ions is opposed by the
potential difference
r.m.p. review
Try here?
can we calculate the potential?
[x]outside
RT
Ex =
ln
[x]inside
zF
this equation determines the voltage at
which the electrical and chemical forces
are balanced; there is NO net movement
of ions.
the Nernst potential for K
if K is 10-fold higher on the inside
[K]o
RT [x]outside 60
Ex =
ln
= z log
= -60 mV
[K]i
zF [x]inside
in excitable cells the RMP is primarily
determined by K ions.………………….but
there are other ions…..
ion
[X]in
[X]out
Eq. (mV)
K
155
4
-98
Na
12
145
+67
Cl
4.2
123
-90
general rule
 relationship between:
membrane potential
ion equilibrium potentials
ENa
+67
membrane
potential (mV)
RMP
ECl
EK
-90
-98
 if the membrane becomes more permeable to
one ion over other ions then the membrane
potential will move towards the equilibrium
potential for that ion (basis of AP). DRIVING
FORCE
 artificial manipulation of MP - reverse direction of
current flow (hence reversal potential)
other ions affect RMP
 different ions have different distributions
 e.g. Na high outside / K high inside
 cell membrane is not uniformly permeable (“leaky”)
to all ions
 relative permeability of an ion determines its
contribution to the RMP
 Goldman-Hodgkin-Katz (GHK) equation
 a small permeability to Na and Cl offsets some of
the potential set up by K
 in reality the cell membrane is a < negative than EK
calculating the true RMP
 driving force on an ion X will vary with MP
 = (Em - Ex)
 Ohm’s law
 V = IR = Ig, or transformed I = gV
 Ix = gx (Em - Ex)
 there will be no current if:
 no channels for ion X are open (no conductance)
 no driving force (MP is at Ex)
chord conductance equation
IK=gK (Em-EK)
INa=gNa (Em-ENa)
ICl=gCl (Em-ECl)
 at steady state:
IK + INa + ICl = 0
 therefore: gK (Em-EK) + gNa (Em-ENa) + gCl (Em-ECl) = 0
gK
gNa
gCl
Em =
E +
E +
E
gK+gNa+gCl K gK+gNa+gCl Na
gK+gNa+gCl Cl
GHK equation
relative permeabilities
ionic concentrations
PK[K]o + PNa[Na]o + PCl[Cl]i
RT
Em =
ln
F
PK[K]i + PNa[Na]i + PCl[Cl]o