Intracellular signal transduction systems do not regulate Na channel in frog ventricular cells

The regulation of sodium channel activity through intracellular signal transduction systems was studied on isolated frog ventricular cells using a whole cell patch-clamp technique. Special care was exercised in evaluating the stability of the voltage-clamp condition by observing shifts in the steady-state inactivation curve (h infinity curve) and changes in series resistance. We applied the following reagents: isoproterenol (Iso; 0.1-10 microM) and forskolin (Fsk; 0.1-10 microM) to activate protein kinase A. 1-Oleoyl-2-acetyl-sn-glycerol (40 microM) and 12-O-tetradecanoylphorbol-13-acetate (80-800 nM) were used to activate protein kinase C, and phenylephrine (0.1-10 microM), dopamine (0.1-10 microM), and histamine (10 microM) were used to stimulate alpha-adrenergic, dopaminergic, and histaminergic receptors, respectively. The current-voltage relationship and the h infinity curve for the sodium channel remained unchanged regardless of the application of these reagents. Iso and Fsk did not affect the sodium current but substantially increased the calcium current, suggesting that the intracellular signal transduction systems remained intact. Therefore, it is concluded that sodium channel in frog ventricular cells is not regulated by intracellular signal transduction systems.