Hormonal Signaling Actions on Kv7.1 (KCNQ1) Channels.

Emely Thompson, Jodene Eldstrom, David Fedida

Journal: Annual review of pharmacology and toxicology 2021;61():381-400

PMID: 32667860

Abstract

Kv7 channels (Kv7.1-7.5) are voltage-gated K channels that can be modulated by five β-subunits (KCNE1-5). Kv7.1-KCNE1 channels produce the slow-delayed rectifying K current, , which is important during the repolarization phase of the cardiac action potential. Kv7.2-7.5 are predominantly neuronally expressed and constitute the muscarinic M-current and control the resting membrane potential in neurons. Kv7.1 produces drastically different currents as a result of modulation by KCNE subunits. This flexibility allows the Kv7.1 channel to have many roles depending on location and assembly partners. The pharmacological sensitivity of Kv7.1 channels differs from that of Kv7.2-7.5 and is largely dependent upon the number of β-subunits present in the channel complex. As a result, the development of pharmaceuticals targeting Kv7.1 is problematic. This review discusses the roles and the mechanisms by which different signaling pathways affect Kv7.1 and KCNE channels and could potentially provide different ways of targeting the channel.

Address: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada; email: [email protected].

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