MECHANISMS OF THE IN-VITRO EFFECTS OF AMPHETAMINE ON RAT SINUS NODE AUTOMATICITY AND MEMBRANE-POTENTIALS OF ATRIAL FIBERS

The main objective of this investigation was to clarify the mechanisms of the acute in vitro actions of amphetamine (AMP) on cardiac electro physiology. Concentrations of AMP ranging from those considered clinic ally therapeutic to those considered toxic were tested in isolated rat sinoatrial tissues while recording membrane potentials with intracell ular microelectrodes. In preparations beating spontaneously, 6.8 nM-2. 71 mu M AMP exerted a positive chronotropic action that was blocked by propranolol. The positive chronotropic action of 5.43 mu M AMP was sm aller than that of 2.71 mu M AMP and was reversed by propranolol. Neit her phentolamine nor atropine blocked this depressant action of AMP. I t is concluded that the positive chronotropic action of AMP was beta-a drenergic and that beta-adrenergic block unmasked a negative chronotro pic action of a high concentration of AMP, which was neither alpha-adr energic nor muscarinic. In atrial fibers driven at a constant rate, 54 .3 nM AMP prolonged the action potential duration (APD), without affec ting the resting membrane potential (RMP), the action potential amplit ude (APA), or the maximum velocity of phase 0, while 5.43 mu M AMP red uced RMP, APA, and the maximum velocity of phase 0, and increased APD. The prolongation of APD, as well as the decreases of RMP and APA, was not abolished by propranolol, phentolamine, or 4-aminopyridine. Conve rsely, nifedipine abolished the effects of AMP on all three parameters . In general, AMP produced mainly a prolongation of the action potenti al. Only a high concentration of AMP decreased RMP and depressed phase 0 of the action potential. The effect of AMP on APD, RMP, and APA ess entially involved increasing the influx of calcium through the L-type channels in the sarcolemma.