Effects of Reserpine and Adrenaline on the Sinoatrial Notched Potential in Rabbit

Abstract

In the course of studies in this laboratory on the mode of action of catecholamines on the transmembrane potential of the extirpated atrium of rabbit (1), some of the poten tials recorded from the pacemaker area (West) responded differently to reserpine and adrenaline from the typical pacemaker potentials. The potential under this study was recorded from the area which was somewhat wider than the triangular pacemaker area shown schematically by West (2). This potential was characteristic in a notching of the upstroke and a slow rate of depolarization, and was very sensitive to reserpine and adre naline. The notched potential in the sinoatrial node of rabbit's heart was at first reported by West (2), who studied the distribution of the potential. Although the similar notched potentials have been reported in the atrioventricular node of mammalian heart (3, 4), the smooth muscle of uterus (5) and the sinoauricular funnel of amphibian heart (6), the exact nature of the potentials remains to be settled. In the present report the responses of the notched potential recorded from the sinoatrial node of rabbit's heart were studied. It is expected that the responses of the potential to reserpine and adrenaline might have some contribution to elucidate the mechanism of the pacemaker activity. METHODSAlbino rabbits, weighing 1.8 to 2.2 kg, were killed through haemorrhage by cutting of both common carotid arteries. The heart was extirpated and the right auricle was separated from the heart. Immediately thereafter, the auricle was fixed on the cork plate immersed in warm (30°C) and 02 saturated modified Tyrode solution. The volume of the solution in the bath was 50 ml. The composition of the modified Tyrode solution is as follows : NaCI 8.6 g, KCl 0.2 g, CaCl, 0.2 g, MgCl2 0.05 g, NaH,P04 0.2 g, Na2HPO4 1.6 g and glucose 1.0 g in 1000 ml. The preparation always showed a rhythmical auto matic contraction for 8 to 14 hours.A glass capillary tube filled with 3 molar KCl solution was used as a different elect rode. As an indifferent electrode a platinum wire immersed in the nutrient solution of the bath was used. The potential changes of the single muscle fiber were recorded follow ing the method of Matsumura and Takaori (7). The potential changes amplified through d.c. amplifier were photographed from a cathode-ray oscilloscope by use of a continuous recording camera. When it was required, the potentials were recorded by use of an ink writing oscillograph.

Effects of Dopamine and Dopa on the Isolated Rabbit’s Atrium Treated With Reserpine

“…The decrease in the rate manifested immediately before the manifestation of the increase but was short lasting. This initial rate-decreasing effect of dopamine resembled to the effect of adrenaline and noradrenaline reported by West (14) and Toda (13). Though the isolated atrium took up noradrenaline when the amine was added to the bath fluid, the addition of dopamine or dopa to the bath fluid did not increase the content of noradrenaline even if the positive inotropic and chronotropic effect had been observed.…”

“…Though the normal isolated atrium took up considerable amounts of noradrenaline added to the bath fluid, the content of noradrenaline in the restrarted heart by noradrenaline did not differ significantly from that in the heart of which spontaneous contraction was totally abolished by the addition of reserpine. From the results Matsuo and Tachi (1) and Toda (13) suggested that the abolishment of the spontaneous contraction and of the transmembrane potentials derived from some mecha nism of action of reserpine other than the catecholamine-depleting effect, and the restart ing effect of adrenaline or noradneraline derived from the pharmacological effect of the amine and not from the biochemical effect such as binding or retaining of the amine at the storage site.…”

The Mode of Action of Reserpine on the Transmembrane Potential of Rabbit’s Atrium in Vitro

“…The right atrium of albino rabbits, weighing 1.8 to 2.2 kg, was isolated following the technique reported previously (1,12), and was mounted on the cork plate in oxygen saturated Tyrode's solution at 30°C. The action potentials were recorded by means of microelectrode filled with 3 M KCI.…”

Effects of 5-Hydroxytryptamine on the Isolated Atrium of Rabbit

“…It was often observed that the increase in the rate by 10-' of adrenaline was about 10% even 30 minutes after the application. (3) The transient decrease in rate followed by the increase in rate was more frequently observed in the atrium in response to 5-HT than that to adrenaline (13,14).…”

“…(30°C) and oxygenated modified Tyrode solution of the composition previously reported (13). The atria were dissected from the ventricles and the right atrium was separated from the left, although the both atria were left intact in the experiment for recording the contraction.…”