title: Gαq and Gα11 contribute to the maintenance of cellular electrophysiology and Ca2+ handling in ventricular cardiomyocytes.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  We conclude that, in a transgenic model, the role of Gα(q) can be best studied using Cre recombinase expression as the molecular determinant for Gα(q) KO rather than tamoxifen/miglyol injection. While excessive hormonal stimulation of the Gα(q)/Gα(11) signalling pathways plays an essential role in cardiac diseases, we propose that the persistent low-level stimulation of these pathways by Gα(q)/Gα(11) activation is instrumental in the physiological behaviour of ventricular myocytes.
authors.affiliation: Institute for Molecular Cell Biology, Saarland University, Homburg/Saar, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Pahlavan
authors.forename: Martin
authors.initials: M
authors.lastname: Oberhofer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sauer
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruppenthal
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Tian
authors.forename: Anke
authors.initials: A
authors.lastname: Scholz
authors.forename: Lars
authors.initials: L
authors.lastname: Kaestner
authors.forename: Peter
authors.initials: P
authors.lastname: Lipp
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D019426:Integrases / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium