Investigating G protein βγ regulation of cardiac Kv7 channels (Miss Lauren McEwan)

The Kv7.1 potassium channel is found in cardiomyocytes where, together with the KCNE1 auxiliary subunit, it forms the IKs current which contributes to the late repolarising phase of the cardiac action potential. Kv7.1/KCNE1 activity is extensively regulated, both basally and in response to β-adrenoreceptor stimulation.

Preliminary data from the applicants’ identified a novel method of regulation of both Kv7.1 and Kv7.1/KCNE1 channels by G protein βγ subunits (Gβγ). Gβγ are known regulators of several ion channels.

The aim of this project is to characterise the role of Gβγ in the regulation of cardiac Kv7 channels both in the basal state and in response to β-adrenoreceptor mediated stimulation. Electrophysiology will be used to investigate Gβγ regulation of Kv7.1 and Kv7.1/KCNE1 dependent currents.

Proximity ligation assay will be used to examine the protein-protein interactions between the channels, Gβγ and other key signalling molecules.

Studies will use a cell overexpression system initially, and then consolidate these findings in human inducible pluripotent stem cell (iPSC)-derived cardiomyocytes.

These experiments will reveal the role of Gβγ in the regulation of cardiac Kv7.1 channels in basal and receptor-stimulated conditions. This will give crucial insight into the regulation of the cardiac action potential in health and disease.