Lecture 15: Major Families of Ion Channels

What are the 4 major functional criteria to classify an ion channel?

• electrophysiology

  • sensitivity

  • voltage-dependence

  • gating behavior

• pharmacology

  • drug/toxin sensitivity

• sensitivity to physiological ligands

  • neurotransmitters

• modulation by intracellular regulators

  • Ca²⁺, cyclic nucleotides

How do you classify K⁺ channels?

• K_v channels (voltage-gated K⁺ channels)

• Large-conductance K_Ca channels (BK)

• Small-conductance K_Ca channels (SK)

• K_ir channels (inward rectifier)

• K2P channels (two core)

What is the primary role of the K⁺ ion channel?

oppose actions of depolarizing Na⁺/Ca²⁺ entry, stabilize resting state by keeping/returning V_m near V_rest

Describe K_V channels.

tetrameric (4 subunits per channel)

Describe Ca_V channels.

The a₁ -subunit consists of 4 domains, with 6 transmembrane regions. The a₂ -subunit has 1 transmembrane domain (delta). The y-subunit has 4 transmembrane-spanning regions.

Describe the Na_V channels.

Has 1 alpha subunit in between two beta subunits. The alpha subunit contains 4 domains consisting of 6 transmembrane-spanning regions each and contains the pore. Each beta subunit has 1 transmembrane domain. The beta subunits are known as auxiliary or pseudosubunits.

Describe the voltage-sensing domain in Na_V, K_v, and Ca_V channels.

the voltage-sensing domain is the S4 subunit. This subunit is positively charged.

What is true of the S4 segment?

• moves outward when V_m depolarizes

• movement cause S6 helices to bend outward, opening pore on alpha subunit

What is true of the pore region?

• binding site for toxins and external blocking molecules (antagonists)

• minimal structure required to form an ion-conducting pore

What is true of the selectivity filter?

determines which types of ion(s) can pass through

How does an ion channel move from closed to open in the ball and chain mechanism (Na⁺ example)?

the ball and chain is hanging down in the intracellular side of the cell. The selectivity filter of the pore region senses Na⁺ and opens the pore allowing for ions to enter the cell.

How does the ion channel go from open to inactive in the ball and chain mechanism (Na⁺ example)?

the ball and chain swings up and sits inside the pore region of the channel blocking flow of ions into the cell. The channel is still in an open conformation.

How does an increase in the concentration of extracellular Ca²⁺ affect the voltage of a cell?

it shifts the voltage activation range to a more positive V_m value

What alters the transmembrane electrical field sensed by Na⁺ channels?

change in extracellular Ca²⁺ concentration

Describe HCN channels.

• Hyperpolarization-activated cyclic nucleotide-gated cation channels

• inward cation current depolarizes V_m

• current is represented by I_h

• Critical roles in cardiac electrophysiology and rhythmic firing of neurons

Describe TRP channels.

• Transient receptor potential cation channels

• TRPV1 - pain and temperature sensation (capsaicin)

• TRPM8 - cold (menthol)