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

Aims Gαq and Gα11 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 Gαq and Gα11 signalling to the basal properties of ventricular myocytes. Methods and results We created a conditional Gαq knockout (KO) after tamoxifen injection into gnaqflox/flox gna11−/− α-MHC Cretg/0 mice and found alterations in the electrophysiological and Ca2+ 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) Gα11 KO, and (iv) Gαq 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 Gαq KO. Myocytes from the Gαq and/or Gα11 KO mice displayed genuine alterations in the action potentials, membrane capacitance, membrane currents, and Ca2+ handling (amplitude, post-rest behaviour, and Ca2+ removal processes). Conclusions We conclude that, in a transgenic model, the role of Gαq can be best studied using Cre recombinase expression as the molecular determinant for Gαq KO rather than tamoxifen/miglyol injection. While excessive hormonal stimulation of the Gαq/Gα11 signalling pathways plays an essential role in cardiac diseases, we propose that the persistent low-level stimulation of these pathways by Gαq/Gα11 activation is instrumental in the physiological behaviour of ventricular myocytes.