Modification of cardiac sodium current by intracellular application of cAMP.

We examined the effects of intracellular perfusion of cyclic adenosine monophosphate (cAMP) on the sodium current (INa) of guinea-pig ventricular myocytes, using the whole-cell clamp technique. INa was elicited by depolarizing voltage steps (-20 mV) from a variety of holding potentials (-120 to -50 mV), under conditions of 60 mM extracellular Na+ concentration ([Na+]o) and at the temperature of 24-26 degrees C. Intracellular perfusion of cAMP decreased the INa elicited from the holding potentials less negative than -90 mV. In the presence of 1 mM cAMP, for example, the peak INa elicited from -80 mV decreased from 6.0 +/- 2.0 nA to 4.0 +/- 2.2 nA (mean +/- SD, P < 0.02, n = 7) within 3-6 min. In the presence of extracellular 3-isobutyl-1-methylxanthine (IBMX, 20 microM), much lower concentrations of cAMP (0.2 mM) yielded a comparable effect. On the other hand, intracellular perfusion of cAMP increased the INa elicited from very negative holding potentials (< -100 mV). For instance, the application of cAMP (1 mM) increased the INa elicited by step depolarizations from -120 mV (to -20 mV), from 9.9 +/- 2.1 nA to 11.0 +/- 3.1 nA (P < 0.05, n = 5). The former effect was attributed to a marked shift of the steady-state inactivation curve of INa to the negative direction; the voltage of half-inactivation shifted from -77.9 +/- 1.0 to -83.5 +/- 1.4 mV, or by -5.6 mV. The latter effect may be explained by increases in maximum available conductance of INa.(ABSTRACT TRUNCATED AT 250 WORDS)