Gsα Protein-Mediated and Protein Kinase A-Independent Regulation of Caveolar Sodium Channels in Rat Cardiomyocytes

In electrophysiological experiments using voltage clamp in the whole-cell configuration and recording of the activity of single channels, extracellular application of 1 mM QX-314 (a derivative of triethyllidocaine) completely and reversibly blocked the sodium conductance through channels in the superficial membranes of rat ventricular cardiomyocytes. After removal of QX-314 from the extracellular medium and in the presence of 22 μg/μl of an inhibitor of protein kinase A (PKA), only the tetrodotoxin-insensitive component of sodium currents was found under conditions of activation of β-adrenoreceptors by isoproterenol (10 μM). In this case, sodium currents activated by isoproterenol were completely inhibited under conditions of intracellular application of monoclonal antibodies against caveolin-3. This observation confirms the hypothesis that an increase in the sodium conductance is, in such cases, mediated by activation of sodium channels belonging to the caveolar pools. The obtained data indicate that subcellular localization of Na_v1.5 channels in caveolar membrane pools of cardiomyocytes can play a special functional role in the enhancement of sodium conductance and modulation of action potentials in rat ventricular cardiomyocytes. Neirofiziologiya/Neurophysiology, Vol. 41, No. 1, pp. 10–18, January–February, 2009.