gates and channels

Question 1

structure of Na_v and K_v

Answer 1

has 4 membrane spanning domains, which contains 6 alpha helices (S1-S6). The 4 domains are linked into a single polypeptide. S4 residue has lys or arg at every third position that sense the voltage. S5 and S6 have a “P loop” form the ion conducting pathway. In K+ the 4 domains are seperate.

Question 2

Channel Selectivity

Answer 2

Charge, Size, some have multiple binding sites to increase sensitivity, selectivity varies (K-v is very selective, Na+_v are not as selective

Question 3

dehydration of the ion

Answer 3

ions must be substantially dehydrated before they pass through the channel pore. This is energetically unfavorable, so the ion interacts with amino acids forming the pore can be positive (lys and arg), negative (glutamate and aspartate), carbonyls (negative), or alpha heliex dipoles (N-terminus positive, C-terminus negative)

Question 4

Na_v and K_v voltage sensors

Answer 4

S4 helices are responsible for voltage sensing, have (+) charged arg and lys at every 3rd position, and translocate in response to changes in voltage across membrane.

Question 5

Na_v and K_v selectivity filter

Answer 5

occurs in a central ion conducting pathway surrounded by S5 and S6 helices and connecting P loop contributed by each of the 4 subunits. extracelular

Question 6

Na_v and K_v activation/inactivation gates

Answer 6

activation corresponds to a hinge-like motion of the S6 segments around a conserved glycine (seen in K_v). Inactivation (Na_v channels) is formed by cytoplasmic loop which connects repeats III and IV. When the linker folds over to the inner end, the channel is closed. both intracellular

Question 7

Sidedness

Answer 7

extracellular has selectivity filter, intracellular has gating. This makes them targets.

Question 8

Tetrodotoxin (TTX)

Answer 8

charged molecule that cannot cross the membrane. It binds to entrance pore of Na_v just above selectivity filter. No effect on intracellular

Question 9

state-dependence

Answer 9

Lidocaine is positively charged at physiological pH and so cannot pass through membranes. Interacts only with intra cellular side. Requires activation gate to be open and inactivation gate to be closed