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 electrophysiology. Concentrations of AMP ranging from those considered clinically therapeutic to those considered toxic were tested in isolated rat sinoatrial tissues while recording membrane potentials with intracellular microelectrodes. In preparations beating spontaneously, 6.8 nM-2.71 microM AMP exerted a positive chronotropic action that was blocked by propranolol. The positive chronotropic action of 5.43 microM AMP was smaller than that of 2.7 microM AMP and was reversed by propranolol. Neither phentolamine nor atropine blocked this depressant action of AMP. It is concluded that the positive chronotropic action of AMP was beta-adrenergic and that beta-adrenergic block unmasked a negative chronotropic action of a high concentration of AMP, which was neither alpha-adrenergic nor muscarinic. In atrial fibers driven at a constant rate, 54.3 nM AMP prolonged the action potential duration (APD), without affecting the resting membrane potential (RMP), the action potential amplitude (APA), or the maximum velocity of phase 0, while 5.43 microM AMP reduced 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. Conversely, nifedipine abolished the effects of AMP on all three parameters. In general, AMP produced mainly a prolongation of the action potential. 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 essentially involved increasing the influx of calcium through the L-type channels in the sarcolemma.
Aileru
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Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, DC 20059, USA.
Carpentier
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RG
D000200:Action Potentials / Q000187:drug effects; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical
D000697:Central Nervous System Stimulants; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D000661:Amphetamine