lecture 4 Flashcards
channelopathies
a disease caused by mutations of ion channels
tetrodotoxin blocks
VG sodium ion channels
hyperkalemic periodic paralysis (HyperKPP)
muscles are excitable cells - VG sodium channels do not inactivate correctly, leading to episodes of stiffness (myotonia) and weakness –> paralysis
L-type calcium channel and Hypokalemic periodic paralysis
voltage sensors are mutated and less responsive to voltage, so less calcium release and not enough muscle contraction
low levels of potassium make it worse bc muscle will repol more quickly
mutations in sodium channels can open up more and make it easy to generate aps which can lead to
epilepsy - an example is GEFS+ - genetic epilepsy with febrile seizures (overactve channels), dravet syndrome (nonfunctional channels) because of Nav 1.1 mutations that shift the voltage curve, in Dravet - nonfunctional channel mutation in INHIBITORY neurons so less inhibition means more sodium
long QT syndrome and what is it linked to
prolonged cardiac action potential that can lead to arrythmias; VG sodium channel due to delayed channel closing and inactivation
hERG mutations
critical in timing to return to the resting state of the cell during cardiac AP – prolong QT interval
cystic fibrosis
disorder with features that reflect mutations in the CF transmembrane conductance regulator gene
chronic bacterial infection
CFTR transports ______ ions
chloride
CFTR is made up of __ domains
5
major mutation in CF
Delta F508, which gets stuck in the ER and it never reaches the cell membrane
CFTR inhibits
ENaC - epithelial Na+ channel
CFTR potentiator drug
Ivacaftor (Kalydeco) - increases chloride transport by increasing the probability of the CFTR channel being open
CFTR corrector drug
Trikafta - improves stability of F508del-CFTR which increases processing and trafficking of mature protein to cell surafce, prevents unfolding of NBS, first triple combination therapy
