Referenced in: none

Automatically associated channels: Slo2

Title: Human slack potassium channel mutations increase positive cooperativity between individual channels.

Authors: Grace E Kim, Jack Kronengold, Giulia Barcia, Imran H Quraishi, Hilary C Martin, Edward Blair, Jenny C Taylor, Olivier Dulac, Laurence Colleaux, Rima Nabbout, Leonard K Kaczmarek

Journal, date & volume: Cell Rep, 2014 Dec 11 , 9, 1661-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25482562

Abstract
Disease-causing mutations in ion channels generally alter intrinsic gating properties such as activation, inactivation, and voltage dependence. We examined nine different mutations of the KCNT1 (Slack) Na(+)-activated K(+) channel that give rise to three distinct forms of epilepsy. All produced many-fold increases in current amplitude compared to the wild-type channel. This could not be accounted for by increases in the intrinsic open probability of individual channels. Rather, greatly increased opening was a consequence of cooperative interactions between multiple channels in a patch. The degree of cooperative gating was much greater for all of the mutant channels than for the wild-type channel, and could explain increases in current even in a mutant with reduced unitary conductance. We also found that the same mutation gave rise to different forms of epilepsy in different individuals. Our findings indicate that a major consequence of these mutations is to alter channel-channel interactions.