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 (I(Na+) 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 I(Na+) evoked by test pulses of 5 ms to a transmembrane potential of 0 mV and its time to peak were analyzed. The availability of I(Na+) was tested with conditioning pulses of 2.5s to potentials between -130 mV and -50 mV. The potential of half-maximal availability was slightly shifted to more negative values by 1-mu-M ISO (2.0 mV, n.s.), as well as by 50-mu-M 8-Br-cAMP (4.0 mV; p < 0.05). The peak amplitude of I(Na+) 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 I(Na+) to 13.3% of the maximal attainable current under control conditions, while ISO decreased I(Na+) to 9.1 % of control (p < 0.1). Corresponding values under the influence of 8-Br-cAMP were 11.4% and 8.3% (p < 0.05). Moreover, in the presence of ISO there was a significant shortening of the time to peak of I(Na+) (0.56 ms to 0.50 ms at -80 mV conditioning potential, p < 0.05) which could not be detected in the presence of 8-Br-cAMP. These observations confirm the assumption of a depressant influence of beta-adrenergic stimulation on cardiac fast sodium inward current also in the depolarized intact myocardium, and suggest that this influence includes cAMP-dependent as well as cAMP-independent pathways.