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Pacemaker selectivity: influence on rabbit atria of ionic environment and of alinidine, a possible anion antagonist
Abstract:
Alinidine, a new compound which reduces heart rate in man and animals, has a selective action on the sinus node. The dose-response relation between alinidine and frequency is not altered by atropine, and alinidine does not block the positive chronotropic action of isoprenaline. Alinidine has no negative inotropic action and has no effect on the linear relation between extracellular Ca and force of myocardial contraction. Alinidine did not alter the slope of the relation between frequency and external calcium concentration. Intracellular recordings showed that alinidine had no effect on the maximum rate of depolarisation or overshoot potential of rabbit atrial muscle, nor was conduction velocity, electrical threshold or maximum follow frequency affected. It was concluded that alinidine did not restrict current through fast inward channels. Alinidine did not increase resting potential or accelerate repolarisation, suggesting that potassium conductance was not increased. The effect of alinidine on frequency was not increased in 14 mmol . litre-1 KCl, or decreased in 2.24 mmol . litre-1 KCl, suggesting that the attachment of alinidine to receptors was not voltage-dependent. Spontaneous frequency was higher when NaCl was replaced by NaBr, and the bradycardic effect of alinidine was increased. Conversely, frequency was lower in NaCH3SO4 and the slope of the dose-response curve decreased. Intracellular recordings from sinus node cells showed that alinidine decreased the slope of the slow diastolic depolarisation and increased action potential duration, without altering the overshoot, the maximum diastolic potential, or the "take-off" potential. A possible explanation for these results is that alinidine restricts current through anion-selective channels. If so, the high potency of alinidine suggests that anionic current normally carries a substantial fraction of the current causing slow diastolic depolarisation.