Electrophysiology

Alberts et al., pp 181-184, Chapter 11
(again, even though there are many classic papers, the text covers a lot so the readings are limited)

History

1791 Luigi Galvani (Italy) - nerve muscle electricity in frog
1840's Carlo Matteuci (Italy) and Emil du Bois Reymond (Germany)
1850 Herman von Helmholtz - speed of conduction (40 m/s)
Walther Hermann Nernst (Germany) (1864-1941) 1920 Nobel in Chemistry
1902 Julius Bernstein apply Nernst, K perm lost in a.p.
1939 K. C. Cole and H. J. Curtis (US) (Transparency) squid
1950's Sir Alan L. Hodgkin & Sir Andrew F. Huxley (Great Britain)
1963 Nobel "ionic mechanisms...excitation inhibition...nerve cell membrane"
Erwin Neher &Bert Sackmann (Germany) for patch clamp (transparency)
Nobel prize in 1992 "incredibly small electric currents that pass
through an ion channel"

Here are the Nobel prize speeches (Neher 1992) (Sakmann 1992) (and I am putting a copy of Neher's on reserve)

Electrical concepts

Circuits (equivalent circuits) Transparency
Battery, anode:+, anions:-, Cathode:-, cations:+
current = i, defined as + to -

Potential (potential difference): V or E
(1) Battery (source of electromotive force, EMF)
(2) Current flow through a resistor
battery and resistor in circuit
E = IR (Ohm's law), R in units of Ohms, W
G is conductance, 1/R, "mho" = Siemens (S)

Membrane capacitance

(another source of impedance)
typically it adds delays (draw) - cuts off high frequency symbol
High pass filter
low pass filter

Glass micropipette typically 1 pf - 10-12f
typically 20 MegOhm
t =RC=2ms (slow)
need negative capacity electrometer to compensate

Sodium - potassium "pump"
Uses 1/3 (2/3 if high electrical activity) of cell
Ouabain binds K+ site (glycoside)
Na+-K+-ATPase
Transparency (Fig. 11-11, p. 515)
"Electrogenic" - imbalance of 3 Na+ - 2 K+ cause current to flow, contribute a few mV
8 membrane spans
homologies with Ca++ pump in sarcoplasmic reticulum
homologies with bacterial K+-ATPase

Ion concentrations

Transparency Table 11-1, p. 508

Derivation of Nernst potential

See Transparency (Panel 11-2, p. 526)
In class, use another Transparency

Assume two compartments in communication
(ions like K+ or Na+ dissolved in each)
Free energy (of each system) = RT ln Ci + ziFF
chemical electrical
F is absolute potential, C is concentration, i is given ion, e.g. K+ or Na+
T is tempreature in degrees Kelvin
R = 8.31 Joules/moleoK
F = 9.65 x 104 Coulombs/mole
= 6.02 x 10 E23 ions/mole (Avagadro's number) x 1.6 x 10E-19 Coulombs/ion (elementary charge) ]
Assume equilibrium which means
(1) no flux
(2) electrical and chemical gradients equal and opposite
(3) energies of two compartments the same
Simple algebra and the fact that log10 = 2.3 x ln gives:
EK+ = 58 log [K+]out / [K+]in

Goldman equation

David Goldman, 1943
assume constant field
Transparency Contributions of Cole and urtis on Squid with AC bridge

Vm = 58 log PK[K+]out + PNa[Na+]out + PCl[Cl-]in
PK[K+]in + PNa[Na+]in + PCl[Cl-]out

Transparency reviews action potential vs. resting potential and permeabilities

Hodgkin-Huxley work

Transparency operational amplifier
voltage clamp
early and late conductances

INa = gNa m3 h (V-VNa)

IK = gK n4 (V-VK)

m and n are "activations" and h is "inactivation"

Sodium channels

how little tetrodotoxin (from puffer fish) does it take to block in lobster nerve
13 / (micro m)2 (Moore et al.)

also Keynes 1971 3.6 x 10E9 channels/cm2
1.5 x 10E-10 Siemens / channel

Reference (only Neher is on reserve right now)

J. W. Moore, T. Narahashi & T.I. Shaw, An upper limit to the number of sodium channels in the nerve membrane? J. Physiol. 1967, 188, 99-105

Neher, E., 1992 Ion channels for communication between and within cells. Science. 256: 498-502.

Sakmann, B., 1992 Elementary steps in synaptic transmission revealed by currents through single ion channels. Science. 256: 503-12.

This page was last updated on Dec. 19, 2002

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