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

Hermann’s 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

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

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 Simultaneously 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

First Recordings of Current by Hodgkin, Huxley, and Katz Ionic Theory of Membrane Excitation Classical Biophysics Period (1935-1952)

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

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

Why are there MANY different types of of Na and K channels even within the same species but across different tissues/organs?

All V-gated Ion Channels – Glycosylation, esp. eukaryotic 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

External Ion Channel Pore Blockers to Isolate gNa vs. gK

Armstrong’s Experiments: Internal TEA Block Incoming K flux knocked out TEAi, therefore must be A Pore! Flux rate determined as 600 ions/millisecond.

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?

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