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

Summary

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 β-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 2.5 s to potentials between −130 mV and −50 mV.

The potential of half-maximal availability was slightly shifted to more negative values by 1 μM ISO (2.0 mV, n.s.), as well as by 50 μM 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 β-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.