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Bi / CNS 150 Lecture 2 Friday, October 4, 2013 Voltage-gated channels (no action potentials today) Henry Lester. The Bi / CNS 150 2013 Home Page. Please note: Henry Lester’s office hours Read the book. If you drop the course, or if you register late,

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Bi / CNS 150 Lecture 2

Friday, October 4, 2013

Voltage-gated channels (no action potentials today)

Henry Lester


The Bi / CNS 150 2013

Home Page

Please note:

Henry Lester’s office hours

Read the book


If you drop the course,

or if you register late,

please email Teagan Wall

(in addition to the Registrar’s cards).

Also, if you want to change sections,

please email Teagan



K+ ion


In the “selectivity filter” of most K+ channels,

K+ ions lose their waters of hydration and are co-ordinated by backbone carbonyl groups

From Lecture 1

Ion selectivity filter


(Like Kandel Figure 5-15)



chemical transmission at




Future lectures:

actually, DE

electric field

electrical transmission in




Major Roles for Ion Channels


The electric field across a biological membrane,

compared with other electric fields in the modern world

1. A “high-voltage” transmission line

1 megavolt = 106 V.

The ceramic insulators have a length of ~ 1 m.

The field is ~ 106 V/m.

2. A biological membrane

The “resting potential” ~ the Nernst potential for K+, -60 mV.

The membrane thickness is ~ 3 nm = 30 Å.

The field is (6 x 10-2 V) / (3 x 10-9 m) = 2 x 107 V/m !!!


From Lecture 1

open channel = conductor


Na+ channel


Max Delbruck

Carver Mead

Richard Feynman

H. A. L





R =


C =

1 mF/cm2



Intracellular recording with sharp glass electrodes

  • = RC = 10 ms;

too large!



A better way: record the current from channels directly?

Feynman’s idea



5 pA = 104 ions/ms

20 ms

A single voltage-gated Na+ channel

-20 mV

-80 mV

Dynamic range

10 ms to 20 min : 108

2 pA to 100 nA

50,000 chans/cell


Press release for 1991 Nobel Prize in Physiology or Medicine:


Simulation of Shaker gating

Francisco Bezanilla's simulation program at the Univ. of Chicago.

“Shaker”, a well-studied voltage-gated K+ channel

“Shaker”, a Drosophila mutant first studied in (the late) Seymour Benzer’s lab

by graduate students Lily & Yuh-Nung Jan (now at UCSF);

Gene isolated simultaneously by L & Y-N Jan lab

& by Mark Tanouye (Benzer postdoc, then Caltech prof, now at UC Berkeley).


The Hodgkin-Huxley formulation of a neuron membrane

Today we emphasize H & H’s description of channel gating

(although they never mentioned channels, or measured a single channel)

Channel opening and closing rate constants are functions of voltage--not of time:

The conformational changes are “Markov processes”.

The rate constants depend instantaneously on the voltage--not on the history of the voltage.

These same rate constants govern both the macroscopic (summed) behavior and the single-molecule behavior.


Demonstrating the Bezanilla model, #1

This channel is actually Shaker with inactivation removed (Shaker-IR).

Based on biochemistry, electrophys, site-directed mutagenesis, X-ray crystallography, fluorescence.

Two of 4 subunits. Outside is always above (show membrane). Green arrows = K+.

C1 and C2 are closed states, A is “active” = open.

6 helices (S1-S6) + P region, total / subunit.

Structure corresponds roughly to slide 7,

The two green helices (S5, S6 + P) correspond to the entire Xtal structure on slide 4.

First use manual opening. Channel opens when all 4 subunits are “A”.

Note the charges in S4 (5/subunit, but measurements give ~ 13 total). Alpha-helix with Lys, Arg every 3 rd residue.

Countercharges are in other helices.

Note the S4 charge movement, “shots”. Where is the field, precisely? Near the top.

Note the “hinge” in S6, usually a glycine.


Demonstrating the Bezanilla model, #2

Read the explanation on the simulation.

Show plot. Manual. Then Voltage (start at default, 0 mV ““delayed rectifier”.

Although we simulate sequentially, the cell adds many channels in parallel.

Not an action potential; this is a “voltage jump” or “voltage clamp” experiment.

Describe shots (measure with fluorescence, very approximately).

I = current. Note three types of I.

Describe gating current (average = I(gate); its waveform does not equal the I(average).

Show -30 mV (delayed openings,) -50 mV (no openings), 0 (default).

Note tail current.

Note I(gate).

There are many V-gated K channels, each with its own V-sens and kinetics.


Inactivation: a property of all voltage-gated Na+ channels

and of

Some voltage-gated K+ channels

Site home:

  • This model is ~ 10 years older than the K+ channel simulation.
  • Na+ channel has only one subunit, but it has 4 internal repeats
  • (it’s a “pseudo-tetramer”).
  • The internal repeats resemble an individual K+ subunit. The “P” region differs, as in Lecture 1, Slide 22.
  • Orange balls are Na+.
  • Note that the single-channel current (balls inside cell) requires two events:
  • All 3 S4 must move up, in response to DV;
  • Open flap. When the flap closes, the channel “inactivates”.
  • The flap may be linked to the 4th S4 domain.
  • The synthesized macroscopic current shows a negative peak, then decays.

Monday’s lecture employs electrical circuits

See also Appendix A in Kandel