PubMed 17305705

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav1.1 , Cav3.1 , KCNQ1 , Kv7.1

Title: Role of cholinergic-activated KCa1.1 (BK), KCa3.1 (SK4) and KV7.1 (KCNQ1) channels in mouse colonic Cl- secretion.

Authors: J E Matos, M Sausbier, G Beranek, U Sausbier, P Ruth, J Leipziger

Journal, date & volume: Acta Physiol (Oxf), 2007 Mar , 189, 251-8

PubMed link:

Colonic crypts are the site of Cl- secretion. Basolateral K+ channels provide the driving force for luminal cystic fibrosis transmembrane regulator-mediated Cl- exit. Relevant colonic epithelial K+ channels are the intermediate conductance Ca2+-activated K(Ca)3.1 (SK4) channel and the cAMP-activated K(V)7.1 (KCNQ1) channel. In addition, big conductance Ca2+-activated K(Ca)1.1 (BK) channels may play a role in Ca2+-activated Cl- secretion. Here we use K(Ca)1.1 and K(Ca)3.1 knock-out mice, and the K(V)7.1 channel inhibitor 293B (10 microm) to investigate the role of K(Ca)1.1, K(Ca)3.1 and K(V)7.1 channels in cholinergic-stimulated Cl- secretion.A Ussing chamber was used to quantify agonist-stimulated increases in short circuit current (Isc) in distal colon. Chloride secretion was activated by bl. forskolin (FSK, 2 microm) followed by bl. carbachol (CCH, 100 microm). Luminal Ba2+ (5 mm) was used to inhibit K(Ca)1.1 channels.K(Ca)1.1 WT and KO mice displayed identical FSK and CCH-stimulated Isc changes, indicating that K(Ca)1.1 channels are not involved in FSK- and cholinergic-stimulated Cl- secretion. CCH-stimulated DeltaIsc was significantly reduced in K(Ca)3.1 KO mice, underscoring the known relevance of this channel in the activation of Cl- secretion by an intracellular Ca2+ increasing agonist. The residual CCH effect observed in K(Ca)3.1 KO mice suggests that yet another K+ channel is driving the CCH-stimulated Cl- secretion. In the presence of the specific K(V)7.1 channel blocker 293B, the residual CCH effect was abolished.This demonstrates that both K(Ca)3.1 and K(V)7.1 channels are activated by cholinergic agonists and drive Cl- secretion. In contrast, K(Ca)1.1 channels are not involved in stimulated electrogenic Cl- secretion.