1-37 Ion channels

Question 1

Ion channel types

Answer 1

1. voltage-gated ion channels: changes in membrane potential affect the probability that channel is open or closed, Na+, K+, Ca+2, Cl- 2. ligand-gated ion channels: receptors for NTs, ATP, exogenous substances, IP3, cAMP, Ca+2 3. leak channels 4. aquaporins ALSO besides channels, can use ion translocation ATPases (pumps), or Uniporters/antiporters/symporters via facilitated diffusion

Question 2

Structure of K-ATP channels

Answer 2

Question 3

K+ channels (3)

Answer 3

Inward rectified: tetramer

Voltage gated: tetramer

Twin pore: dimer

Question 4

Role of K-ATP channels in insulin secretion

Answer 4

Inhibited by intracellular ATP, sulfonylurea receptors (subunit that aassociated with K+ inward rectifying channel) provide binding site for ATP

If ATP levels low, KATP chanels become activated and cause K+ efflux leading to membrane hyperpolarization and reduction in the energy consuming work of ion pumps.

If ATP levels high, inhibit KATP channel, leading to membrane depolarization and secretion of insulin. Sulfonylureas are diabetic drugs that inhibit and allow for increased insulin secretion.

Question 5

K-ATP channels in vascular smooth muscle

Answer 5

Question 6

voltage gated K+ channel inactivation motifs

Answer 6

Question 7

Basic structure of Na+ and Ca+2 channels

Answer 7

Question 8

Functional states of voltage-gated Na+ channels

Blockers

Answer 8

local anestatics block these channels by interacting with the inactivated state of the channel, can act from inside the cell to box out Na+ from entering the channel inside the cell

tetrodotoxin: puffer fish fugu, blocker

Algae bloom: saxitoxin, brevetoxin A

Question 9

Voltage-gated Ca+2 channels overview

Answer 9

Either low-voltage activated (T type) or high-voltage activated (L type) based on the membrane potential theshold required for opening the channels.

L-type channels: blocked by dihydropyridines, phenylalkylamines, benzothiazepines to treat hypertension, MI, arrhythmia

T-type channels: treat epilepsy

Indirect Ca+2 voltage gated channel inhibitors: gabapentinoids, interact with auxillary subunit of the channel and treat neuropathic pain

Question 10

Antiarrhythmic drug effects (Na,Ca,K channel blockers)

Answer 10

Question 11

Drug induced cardiac arrythimia

Answer 11

accidentally blocks HEGR: results in long QT syndrome, yikes

Question 12

voltage gated K+ channels: cardiac, brain

Answer 12

cardiac: hERG responsible for rapid delayed rectifier current (I-Kr) and is a target for antiarrhythmics, blocking this current slows repolarization of cardiac AP and prolongs the effective refractory period thus suppressing arrhythmia caused by reentry
* also I-Kr is unintended traget of non-cardiac drugs that cause unwanted cardiac toxicity and now FDA screens all drugs for this
brain: targets for anticonvulsant drugs, channels activated which generate a M-current are targeted by antiepileptics. M-currents generates a repolarizing current in neurons that dampens excitability