Action Potentials in Different Nerve Membranes

1
Action Potentials in Different Nerve Membranes AP
A membrane potential change caused by a flow of
ions through ion channels in the membrane
Intracellular Recording Two Points, Ea and
Eb Conduction Velocity (cv) Probagation
time/distance between a and b Node of
Ranvier Depolarize then Spike Motoneuron, Squid
Axon Shocked away from a Latency is distance
Traveled. Conduction Velocity but Not Channel
Conductance is Temperature Dependent
2
Hermanns Cable Theory Passive spread of
APs Similar to a Leaky Telegraph Cable Re
extracellular membrane resistance Ri
cytoplasmic membrane resistance Rm variable
dependent upon channel gating that causes change
in emf Cm membrane as parallel plate capacitor
These two elements may be just different aspects
of the same membrane mechanism Cole and Curtis
1938
3

• Action Potentials
• 1, Underlying ionic basis Na and K channels
• All or none
• Propagated by passive spread of electrotonic
  currents
• Restriction of ion channel expression Example
  Node of Ranvier and Saltatory Conduction
• Nav1.6 and Kv1.2 (See Plate 1)
• Ion channels have no thresholds for activation.
  AP 15 TH
• Code is not in the width or height of the AP
  Information code The Frequency

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Voltage-clamp Electrophysiology Approach is
Preparation Dependent Best Biophysical
Technique to Study Ion Channel Activity
E recording electrode I current injecting
electrode FBA feedback amplifier (Px changes
can be rapid and FBA with high freq. response has
to readjust the current injection constantly
) Principle Vc is set by investigator Simultan
eously Acts as a Voltage Sensor (E) and
Current Injector (I) Best Utility for These
3 Two Microelectrode Suction Pipette Patch
Clamp
Im Ii Ic Ii Cm dE
dt
5
First Recordings of Current by Hodgkin, Huxley,
and Katz Ionic Theory of Membrane
Excitation Classical Biophysics Period (1935-1952)
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The Independence Relation First recognized that
current could be separated into components
carried by different ions.
First to use the approach of Ion Substitution
1. Observed Biphasic Current when
Hyperpolarized. 2. Choline Chloride
for Nao 3. Algebraic Difference To Derive the
INa
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HH Model to Determine the H Infinity Curve for Na
Channel Inactivation
Activation rapid process that opens Na channels
during a depolarization Inactivation process
that closes Na channels during a depolarization
must repolarize membrane to release channels from
inactivated state Recovery from Inactivation
Curves
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Why are there MANY different types of of Na and K
channels even within the same species but across
different tissues/organs?
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Na Channels Alpha, Beta1, Beta 2

• Ca Channels
• Alpha1, alpha2, beta, gamma, delta

K Channels 4 Alpha Beta

• All V-gated Ion Channels
• Glycosylation, esp. eukaryotic
• Principle and Auxillary subunits
• a. Principle
• toxin-binding sites
• S4 voltage sensor
• pore
• gate
• selectivity filter
• b. Auxillary
• membrane trafficking to the PM
• alteration of inactivation
• 3. Protein-protein interactions

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External Ion Channel Pore Blockers to Isolate gNa
vs. gK
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Armstrongs Experiments Internal TEA
Block Incoming K flux knocked out TEAi, therefore
must be A Pore! Flux rate determined as 600
ions/millisecond.
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Myelination allowed increase conduction velocity
of APs through Saltatory Conduction across the
Nodes of Ranvier Localization of Ion Channels
Nav1.6 and Kv1.2 (See Plate 1)
Tau Rm x Cm How did invertebrate organisms
increase conduction velocity? What is the
evolutionary advantage of myelin?
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Do Current Biophysical Properties Deliniate a
Different Gene?
Human gene names all capital letters Non-human
mammalian lower case Gene names are always in
italics