Gαq and Gα11 contribute to the maintenance of cellular electrophysiology and Ca2+ handling in ventricular cardiomyocytes

Cardiovascular Research
Sara PahlavanPeter Lipp

Abstract

Gα(q) and Gα(11) signalling pathways contribute to cardiac diseases such as hypertrophy and arrhythmia, but their role in cardiac myocytes from healthy hearts has remained unclear. We aimed to investigate the contribution of Gα(q) and Gα(11) signalling to the basal properties of ventricular myocytes. We created a conditional Gα(q) knockout (KO) after tamoxifen injection into gnaq(flox/flox) gna11(-/-) α-MHC Cre(tg/0) mice and found alterations in the electrophysiological and Ca(2+) handling properties of ventricular myocytes using patch-clamp and Fura-2 video imaging. To reveal the genuine effects of protein KO, we investigated the individual contributions of (i) tamoxifen injection, (ii) Cre recombinase expression, (iii) Gα(11) KO, and (iv) Gα(q) KO. Profound and persistent alterations in myocyte properties occurred following the tamoxifen injection alone. Consequently, we used the presence or absence of Cre recombinase expression as the determinant for the Gα(q) KO. Myocytes from the Gα(q) and/or Gα(11) KO mice displayed genuine alterations in the action potentials, membrane capacitance, membrane currents, and Ca(2+) handling (amplitude, post-rest behaviour, and Ca(2+) removal processes). We conclude that, in a transgenic mod...Continue Reading

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Citations

Oct 18, 2015·International Journal of Cardiology·Kathrina WiesenLars Kaestner
May 9, 2014·Circulation Research·Lars KaestnerPeter Lipp
Oct 16, 2018·Cardiovascular Research·Elisabeth KaiserPeter Lipp
Nov 7, 2016·Cellular and Molecular Life Sciences : CMLS·Danielle KamatoPeter J Little

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