1

Voltage-Gated Ion Channel: Activation States

Li+

Ca2+,Cl-,K+, Na+-Channels

In the closed resting state, the cell membrane is polarized, the extracellular portion of the pore is closed while the intracellular gating mechanism remains open. Upon activation, the membrane depolarizes, opening the extracellular portion of the pore and allowing the ion to enter the cell. The refractory period occurs while the membrane is still depolarized, the gating mechanism has closed the intracellular portion of the pore, rendering the channel inactive.

2

Ligand-Gated Ion Channel: Structure and Activation States

A) The intrinsic ion channel in this superfamily of receptors undergoes a conformational change following the binding of an extracellular ligand to its binding site, which allows for the opening of the channel pore.

B) The pore is formed by a pentameric arrangement of subunits, which are in turn composed of a large extracellular domain (which contains

the ligand binding site) and four transmembrane domains.

Li+nAcChR, Serotonin, GABAAR, incl.

3

Calcium Channel Structure

A) The 1 subunit is comprised of four homologous domains, each of which contains six transmembrane helices. The subunit is intracellular and associates with the 1 subunit. The subunit is a glyoprotein that possesses four transmembrane segments. The 2 subunit is extracellular, highly glycosylated and associates with the membrane spanning subunit via disulfide bonds.

B) The four domains of the 1 subunit cluster in the membrane to form the pore region.

Li+

4

Schematic Representation of the HCN Channel

Li+-Hyperpolarization-Activated Cyclic Nucleotide-Gated-

Cation-Channel (Na+ ,K+)

5

2TM Potassium Channel Structure

6TM Potassium Channel Structure

Li+

Li+

Four of these subunits cluster to form the active channel. Each subunit is composed of two membrane-spanning

helices connected by a P loop. A) A) The subunit is formed from 6 transmembrane segments and is associated with a regulatory subunit.

B) Four subunits form the pore.

6

Sodium Channel Structure

Li+

A) The subunit consists of four domains of six transmembrane segments, with the 5th and 6th segments comprising the pore formation unit. The subunits consist of a single membrane spanning segment with an immunoglobulin-like fold in an extracellular domain. The subunit contains the binding sites for a variety of toxins and drugs, as indicated.

B) The four domains of the subunit form the pore within the membrane.