Influence of beta-adrenergic stimulation on the fast sodium current in the intact rat papillary muscle

The loose-patch-clamp technique was used on intact cardiac papillary muscle of the rat to examine whether the fast sodium inward current (INa+) is influenced by the beta-adrenergic stimulant isoproterenol (ISO) or by 8-bromo-3',5'-cyclic adenosine monophosphate (8-Br-cAMP), respectively. The amplitude of INa+ evoked by test pulses of 5 ms to a transmembrane potential of 0 mV and its time to peak were analyzed. The availability of INa+ was tested with conditioning pulses of 2.5 s to potentials between -130 mV and -50 mV. The potential of half-maximal availability was slightly shifted to more negative values by 1 microM ISO (2.0 mV, n.s.), as well as by 50 microM 8-Br-cAMP (4.0 mV; p less than 0.05). The peak amplitude of INa+ elicited from strongly negative potentials was increased by ISO (18%, n.s.), while 8-Br-cAMP exerted no directional effect. Depolarizing conditioning pulses (-60 mV) decreased INa+ to 13.3% of the maximal attainable current under control conditions, while ISO decreased INa+ to 9.1% of control (p less than 0.1). Corresponding values under the influence of 8-Br-cAMP were 11.4% and 8.3% (p less than 0.05). Moreover, in the presence of ISO there was a significant shortening of the time to peak of INa+ (0.56 ms to 0.50 ms at -80 mV conditioning potential, p less than 0.05) which could not be detected in the presence of 8-Br-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)