동방결절 활동전압에 대한 아데노신 효과

• 영문명: Effects of Adenosine on the Action Potentials of Rabbit SA Nodal Cells
• 발행기관: 대한생리학회
• 저자명: 김기환(Kim, Ki-Whan) 호원경(Ho, Won-Kyung)
• 간행물 정보: 『대한생리학회지』제18권 제1호, 19~36쪽, 전체 18쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1984.06.30

영문 초록

Since the first report of Drury and Szent-GyÖrgyi in 1929, the inhibitory influences of adenosine on the heart have repeatedly been described by many investigators. These studies have shown that adenosine and adenine nucleotides have overall depressant effects, similar to those of acetylcholine. Heart beats become slow and weak. It is also well known that adenosine is a potent endogenous coronary vasodilator. Many investigations on the working mechanisms of adenosine have been focused mainly on the effects of the coronary blood flow. However, the cellular mechanisms underlying the inhibitory action of adenosine on sinus node are not well understood yet. Thus, this study was undertaken to examine the behavior of rabbit SA node under influence of adenosine. In these series of experiments three kinds of preparations were used: whole atrial pair, left atrial strip, and isolated SA node preparations. The electrical activity of SA node was recorded with conventional glass microelectrodes 30 to 50 MΩ. The preparations were superfused with bicarbonate-buffered Tyrode solution of pH 7.35 and aerated with a gas mixture of 3% CO₂-97% O₂ at 35℃. In whole atrial pair, adenosine suppressed sinoatrial rhythm in a dose-dependent manner. Effect of adenosine on atrial rate appeared at the concentration of 10^-5M and was enhanced in parallel with the increase in adenosine concentration. Inhibitory action of adenosine on pacemaker activity was more prominent in the preparation pretreated with norepinephrine, which can steepen the slope of pacemaker potential by increasing permeability of Ca⁺². Calcium ions in perfusate slowly produced a marked change in sinoatrial rhythm. Elevation of the calcium concentration from 0.3 to 8 mM increased the atrial rate from 132 to 174 beats/min, but over 10 mM Ca⁺² decreased. The inhibitory effect of adenosine on sinoatrial rhythm developed very rapidly. Atrial rate was recovered promptly from the adenosine-induced suppression by the addition of norepinephrine, but extra Ca⁺² was less suitable to restore the suppression of atrial rate. Adenosine suppressed also atrial contractility in the same dosage range that restricted pacemaker activity, even in the reserpinized preparation. In isolated SA node preparation, spontaneous firing rate of SA node at 35℃(mean±SEM, n=16) was 154±3.3 beats/min. The parameters of action potentials were: maximum diastolic potential(MDP), -73±1.7 mV: overshoot(OS), 9±1.4 mV: slope of pacemaker potential(SPP), $94±3.0 mV/sec. Adenosine suppressed the firing rate of SA node in a dose-dependent manner. This inhibitory effect appeared at the concentration of 10^-6M and was in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until 10^-4M. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine and propranolol. Lowering extra Ca²⁺ irom 2 mM to 0.3 mM resulted in a marked decrease of OS and SPP, but almost no change of MDP. However, increase of perfusate Ca²⁺ from 2 mM to 6 or 8 mM produced a prominent decrease of MDP and a slight increase of OS and SPP. Dipyridamole(DPM), which is known to block the adenosine transport across the cell membrane, definately potentiated the action of adenosine. The results of this experiment suggest that adenosine suppressed pacemaker activity and atrial contractility simultaneously and directly, by decreasing Ca²⁺-permeability of nodal and atrial cell membranes.