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 u sing 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 c hanges in series resistance. We applied the following reagents: isopro terenol (Iso; 0.1-10 mu M) and forskolin (Fsk; 0.1-10 mu M) to activat e protein kinase A. 1-Oleoyl-2-acetyl-sn-glycerol (40 mu M) and 12-O-t etradecanoylphorbol-13-acetate (80-800 nM) were used to activate prote in kinase C, and phenylephrine (0.1-10 mu M), dopamine (0.1-10 mu M), and histamine (10 mu M) were used to stimulate alpha-adrenergic, dopam inergic, and histaminergic receptors, respectively. The current-voltag e relationship and the h infinity curve for the sodium channel remaine d unchanged regardless of the application of these reagents. Iso and F sk did not affect the sodium current but substantially increased the c alcium current, suggesting that the intracellular signal transduction systems remained intact. Therefore, it is concluded that sodium channe l in frog ventricular cells is not regulated by intracellular signal t ransduction systems.