Lecture 15: Major Families of Ion Channels

What are the four functional criteria for ion channel classification?

• electrophysiology: selectivity, voltage-dependence, and gating behavior

• pharmacology: drug/toxin sensitivity

• sensitivity to physiological ligands

• modulation by intracellular regulators

True or False: The same P_O can be achieved with different opening/closing times and patterns.

true

What is the largest, most diverse family of ion channels?

K+ channel classification

What are the primary roles of K+ channels?

• oppose actions of depolarizing Na+/Ca2+ entry

• stabilize resting state by keeping/returning V_m near V_rest

What are the five distinct families of genes?

• 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-pore)

What is the structure of K_v channels?

tetrameric (4 subunits per channel)

What is the structure of Ca_v channels?

pseudotetrameric structure

What is the structure of Na_v channels?

pseudotetrameric structure with alpha and beta subunits

What are the functions of the B subunit on the Na_v channels?

modify gating behavior and membrane localization

Which channels contain a voltage-sensing domain?

• Na_v

• Ca_v

• K_v

What is the charge on the S4 segment?

positively charged

What does S4 do when V_m depolarizes? What does this cause?

moves outward—causing S6 helices to bend outward and open the pore

What is the function of the pore region?

the binding site for toxins and external blocking molecles (antagonists)

True or False: There is minimal structure required to form an ion-conducting pore.

true

What is the function of the selectivity filter?

determines which types of ion(s) can pass through

Describe the ball-and-chain mechanism of inactivation.

• 3 states: closed, open, and inactivated

• closed and open states are reversible by depolarization and hyperpolarization

• open state → inactivated state

• inactivated → closed state

• closed state: channel is closed and ball-and-chain is in the cytosol

• open state: channel is open and ball-and-chain is in the cytosol

• inactivated state: channel is open and ball-and-chain blocks the pore

What affects voltage-dependence of Na+ channel gating?

extracellular Ca2+ concentration

How does extracellular Ca2+ concentration affect Na_v channels?

the change in extracellular calcium concentration alters transmembrane electrical field sensed by the Na+ channel

What does an increase in extracellular calcium concentration lead to?

the voltage activation range shifts to more positive V_m values

What do HCN channels stand for?

hyperpolarization-activated, cyclic nucleotide-gated cation channels

What is the current mediated by HCN channels?

I_h

True or False: Inward cation currents through HCN channels depolarizes the V_m.

true

What areas do HCN channels play critical roles in?

• cardiac electrophysiology

• rhythmic firing of neurons in the brain

True or False: HCN channels are sensitive to cAMP levels.

true

What do TRP channels?

transient receptor potential cation channels

What is the ligand for TRPV1? What does this ligand signal?

capsaicin; pain and temperature sensation

What is the ligand for TRPM8? What does this ligand signal?

methanol; mint and cool temperatures