Essential role of diastolic oscillatory potentials in adrenergic controlof guinea pig sino-atrial node discharge

摘要

Background: The diastolic oscillatory after-potential Vos and pre-potential ThVos play an essentialrole in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigatewhether these oscillatory potentials are also involved in adrenergic control of SAN discharge.Methods: Vos and ThVos were visualized by superfusing guinea pig SAN in high [K+]o. The actionsof adrenergic agonists on oscillatory potentials were studied by means of a microelectrodetechnique. Statistical significance was determined by means of Student's paired t-test.Results: In non-spontaneous SAN, norepinephrine (NE) decreased the resting potential into avoltage range ("oscillatory zone") where increasingly larger ThVos appeared and initiatedspontaneous discharge. In slowly discharging SAN, NE gradually increased the rate by increasingthe amplitude and slope of earlier-occurring ThVos and of Vos until these oscillations fused withinitial diastolic depolarization (DD1). In the presence of NE, sudden fast rhythms were initiated bylarge Vos that entered a more negative oscillatory zone and initiated a large ThVos. Recovery fromNE exposure involved the converse changes. The β-adrenergic agonist isoproterenol had similaractions. Increasing calcium load by decreasing high [K+]o, by fast drive or by recovery in Tyrodesolution led to growth of Vos and ThVos which abruptly fused when a fast sudden rhythm wasinduced. Low [Ca2+]o antagonized the adrenergic actions. Cesium (a blocker of If) inducedspontaneous discharge in quiescent SAN through ThVos. In spontaneous SAN, Cs+increased Vosand ThVos, thereby increasing the rate. Cs+ did not hinder the positive chronotropic action of NE.Barium increased the rate, as Cs+ did.Conclusion: Adrenergic agonists: (i) initiate SAN discharge by decreasing the resting potential andinducing ThVos; (ii) gradually accelerate SAN rate by predominantly increasing size and slope ofearlier and more negative ThVos; (iii) can induce sudden fast rhythms throug