+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Regulation of caveolar cardiac sodium current by a single Gsalpha histidine residue.

      American Journal of Physiology - Heart and Circulatory Physiology

      metabolism, Sodium Channels, Sodium, drug effects, Receptors, Adrenergic, beta, Rats, Sprague-Dawley, Rats, pharmacology, Protein Kinase Inhibitors, Protein Conformation, Protein Binding, Patch-Clamp Techniques, NAV1.5 Voltage-Gated Sodium Channel, enzymology, Myocytes, Cardiac, Mutation, Mutagenesis, Site-Directed, Models, Molecular, Membrane Potentials, Male, Isoproterenol, Ion Channel Gating, Histidine, genetics, chemistry, GTP-Binding Protein alpha Subunits, Gs, antagonists & inhibitors, Cyclic AMP-Dependent Protein Kinases, Caveolin 3, Caveolae, Animals, Adrenergic beta-Agonists

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Cardiac sodium channels (voltage-gated Na(+) channel subunit 1.5) reside in both the plasmalemma and membrane invaginations called caveolae. Opening of the caveolar neck permits resident channels to become functional. In cardiac myocytes, caveolar opening can be stimulated by applying beta-receptor agonists, which initiates an interaction between the stimulatory G protein subunit-alpha (G(s)alpha) and caveolin-3. This study shows that, in adult rat ventricular myocytes, a functional G(s)alpha-caveolin-3 interaction occurs, even in the absence of the caveolin-binding sequence motif of G(s)alpha. Consistent with previous data, whole cell experiments conducted in the presence of intracellular PKA inhibitor stimulation with beta-receptor agonists increased the sodium current (I(Na)) by 35.9 +/- 8.6% (P < 0.05), and this increase was mimicked by application of G(s)alpha protein. Inclusion of anti-caveolin-3 antibody abolished this effect. These findings suggest that G(s)alpha and caveolin-3 are components of a PKA-independent pathway that leads to the enhancement of I(Na). In this study, alanine scanning mutagenesis of G(s)alpha (40THR42), in conjunction with voltage-clamp studies, demonstrated that the histidine residue at position 41 of G(s)alpha (H41) is a critical residue for the functional increase of I(Na). Protein interaction assays suggest that G(s)alphaFL (full length) binds to caveolin-3, but the enhancement of I(Na) is observed only in the presence of G(s)alpha H41. We conclude that G(s)alpha H41 is a critical residue in the regulation of the increase in I(Na) in ventricular myocytes.

          Related collections

          Author and article information



          Comment on this article