Mechanisms Underlying the Dual Effect of Polyunsaturated Fatty Acid Analogs on Kv7.1.

ABSTRACT: Polyunsaturated fatty acid (PUFA) analogs represent a new class of potential anti-arrhythmic K_V7.1 and K_V7.1+KCNE1 channel activators. In this study, we describe dual independent activating effects of negatively charged PUFA analogs on K_V7.1 and K_V7.1+KCNE1 that are dependent on discrete channel motifs. PUFA analogs are critically dependent on K326 in S6 of K_V7.1 to increase the maximum conductance and critically dependent on specific S4 arginines in K_V7.1 to shift the voltage dependence of channel opening toward negative voltages. Our findings provide insights into how K_V7.1+KCNE1 activators may interact electrostatically both with the pore domain and the voltage-sensing domain to augment channel activity. We bel

SUBMITTER: Liin SI 

PROVIDER: S-EPMC6190921 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature