DR Medhat MRCP

هام جدا Examples of ion channels & their related diseases and drugs
Ion channels
Epithelial ion channels
Epithelial sodium channel (ENaC) Cystic fibrosis transmembrane
regulator (CFTR)
Site In the apical (luminal) membrane of Luminal membrane of epithelium of
absorptive epithelium e.g DCT & CD. airway ,pancreatic duct & sweat gland
Subunits α, β & ϒ subunits. 2 repeating structures
Domains (proteins)
Function Re-absorption of Na from the urine to Help Na & Cl (with H 2 O) secretion
the interstitium which in DCT
into the lumin of airway & pancreatic
promotes K + excretion in urine
duct (i.e surface liquid) & vice
Control ++ by aldosterone Na +
reabsorption & K + excretion in DCT
- - by ANP ( Na reabsorption)
Disease
related Liddle`s Pseudohypoaldosteronism
syndrome
(I)
AD mutation AR mutation in ENaC
s. Na , HTN s. Na , hypotension
-- RAS ++ RAS
Hypokalemia Hyperkalemia
Non-epithelial ion channels
Voltage-gated sodium channels
In the membranes of skeletal
ms, cardiac ms & nerve cells
α,β subunits.
Role in action potential :
- RMP : channels are closed
- Depolarization : rapid open.
‏(خد بالك versa in sweat glands
- Repolarisation : inactivated
CFTR gene on chromosome 7. In skeletal muscles :
o Small mutation in α-
subunit Myotonia
Cystic fibrosis (AR mutation of CFTR)
Airway : viscid secretion blocking
airway ,causing bronchiectasis &
recurrent lung infection.
Pancreatic duct : obstruction causing
mal-absorption (no pancreatic
enzymes) ,wt loss & DM (30%)
هام Sweat gland : Nacl in sweat
o Severe mutation
periodic paralysis
In cardiac muscles : α
subunit mutation
o Long Q-T syndrome
o Torsade de pointes.
In nerve cell : β1 mutation
o Familial Epilepsy.
Drug
targeting
Amiloride : -- ENaC Na
reabsorption so Na loss & K
excretion (ttt of liddle)
No specific drugs act on CFTR.
Membrane stabilizers used in
dysrrhythmia &epilepsy block
voltage gated Na ch. e.g class I
anti-arrhythmics &phenytoin