Beruflich Dokumente
Kultur Dokumente
Idan Segev
Lesson #4
Electrifying brains active electrical signals
Spike in axon the spike
Axial electrode
mm 0.5~
First direct (intracellular) recorded action-
32 potential (spike)
in the squid giant axon (Hodgkin and Huxley,
1939)
Following sufficient
depolarization
)all or none(
mV 100
msec
Figure4.1 First direct measurements of membrane potential in squid giant axon. (A) Capillary tube
with sea water has been carefully pushed down axon and serves as electrode to measure potential differ
across membrane(after Hille1984). (B) MembranevoltageVm (inmV) during action potential. Timeindic
The H&H equations for spike initiation
The triumph of theory
Supra-
current stimuli
threshold
Sub-
threshold
clamp)
The technique that made the whole difference
Space clamp - making the (long) axon effectively isopotential via the
.insertion of an axial conductive wire
8
inward 04:11:08 PM
Separating voltage-dependent active (excitable)
currents
Using pharmacological agents
different currents flow via the membrane 2
during the spike TTX blocks the early fast inactivat
current
Tetrodotoxi
n
)TTX(
outwar
d
inward
9 04:11:08 PM
Separating voltage-dependent active (excitable)
currents
Using pharmacological agents
different currents flow via the membrane 2
during the spike TEA blocks the late slow non-inactiva
current
Tetraethilammoniu
m
)TEA(
outwar
d
inward
10 04:11:08 PM
Changing ion concentration at bath with giant axon
showed that early current is carried by Na+ ions and
late one by K+ ions
Outwar
d K+
current
Inward Na+
current
11 04:11:08 PM
The electrical circuit for the squid axon (excitable)
membrane
Ion currents (K+ and Na+) for various depolarizing
voltage clamp
( and extracting respective ion conductances)
IK = gK (Vm EK); INa = gNa (Vm ENa)
Vm
13 04:11:08 PM
Fitting an equation for the K current (K-conductance)
during/following VC
K-current in response to a
step voltage clamp of 25 mV
(upstroke) slow rise
following the VC and faster
decay at the end of the VC
n gate
n gate
+
K +
K
INSIDE INSIDE
The activation function, n, and the rate functions
n and n
Similar procedure is used to extract the activation (m) and inactivation
(h) parameters for the Na current
18 04:11:09 PM
Fitting Na current for different VC depolarizing values
Graphical interpretation of H&H model for
Na channel (by 3
the Na channel Open Na channel
activated m gates and
1 inactivated h gate)
Na outside
m gate
m( fast )3
m gate
(activated) gates
m gate open with
depolarization
h( slow )1
(inactivated) gate
h gate closes with
depolarization
Voltage-dependent Ion channels underlying the AP
(later than H&H)
21 04:11:09 PM
dt
Overlay of the action potential (voltage) and underlying Na
and K conductances
23 04:11:09 PM
Model verication
Model
Experimen
t
The refractory period
Model
Experimen
t
H&H explanation for the
refractory period
Refractory period