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Ion Channels and Pumps


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top view

Example: one of many types of K+ channel

side view

25 250 K Dalton

protein complexes

Coil up, insert into

membrane

Consist of multiplesubunits (same or

different)

Each subunit consists of

several membrane-

spanning regions

Channel forms a water-filled pore through which

ions flow passively (i.e.

not requiring energy)

What is an ion channel

physically?


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Ion channels are composed of

several subunits

Note about physical distribution of channels in a cells plasma membrane:

A 10 um diameter cell is like a basketball made out of office paper

Example: voltage-dependent Na+ channels occur at density of ~2/um^2


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Each subunit has multiple

membrane-spanning regions


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Are ion channels

selective?

Some no (as in certain

bacterial toxins)

Most are highly selective

Important ones in the brain:

Na+, K+, Cl-, Ca++, +mixed Despite selectivity, they may

conduct up to 100 million

ions per second

Selectivity can be

mediated:

by size

by molecular sieve

Most ion channels are highly selective


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Ion channels can be gated in multiple ways

Gating can

occur: by voltage

mechanically

by chemical ligand

(outside the cell) by phosphorylation

(inside the cell)

or not gated at all

Gating involves:

A local conformational

change

or a global structural

change

or a gating particle


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Channels can be modeled as linear resistors


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But truth be told, ion channels are not reallylinear,

but in this class we pretend.

Acts like higherconductance whenflowing from high[C] to low [C]

Determining K+ channel activation curves from K+ channel currents often requires the Goldman-Hodgkin-Katz equation

John R. Clay *http://www.frontiersin.org/cellularneuroscience/paper/10.3389/neuro.03/020.2009/
http://www.frontiersin.org/cellularneuroscience/paper/10.3389/neuro.03/020.2009/http://www.frontiersin.org/cellularneuroscience/paper/10.3389/neuro.03/020.2009/


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Note: channels are generally either open or closed, but the

open probability can vary continuously, so at a population

level, ionic conductances look continuous


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By contrast, a pump burns ATP


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Ion Selectivity Is Based On Dehydration Energy

Profiles

K+

H

OH

Na+

H

OH

K+Na+

hydrated Na+ orhydrated K+ orKcsA-hydrated K+

KcsA-hydrated Na+

DG = 5-10 kcal/mol

Selectivity filters of channel subunits

Ionic radius of K+: 1.33 Ionic radius of Na+: 0.95


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Potassium Ions Are Transported In The Dehydrated Form

Zhou et al. (2001)

Crystal structures contain two K+ ions separated by a water molecule, either as K-water-K-water, or as water-K-water-K.

High throughput is due to destabilization of the ion-protein binding by mutual repulsion between a bound ion and an

approaching ion.

Ion Channels and Pumps

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