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

Abstract

Abstract

Background: The diastolic oscillatory after-potential Vos and pre-potential ThVos play an essential role in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigate whether 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 actions of adrenergic agonists on oscillatory potentials were studied by means of a microelectrode technique. Statistical significance was determined by means of Student's paired t -test.

Results: In non-spontaneous SAN, norepinephrine (NE) decreased the resting potential into a voltage range ("oscillatory zone") where increasingly larger ThVos appeared and initiated spontaneous discharge. In slowly discharging SAN, NE gradually increased the rate by increasing the amplitude and slope of earlier-occurring ThVos and of Vos until these oscillations fused with initial diastolic depolarization (DD1 ). In the presence of NE, sudden fast rhythms were initiated by large Vos that entered a more negative oscillatory zone and initiated a large ThVos . Recovery from NE exposure involved the converse changes. The β-adrenergic agonist isoproterenol had similar actions. Increasing calcium load by decreasing high [K+ ]o , by fast drive or by recovery in Tyrode solution led to growth of Vos and ThVos which abruptly fused when a fast sudden rhythm was induced. Low [Ca2+ ]o antagonized the adrenergic actions. Cesium (a blocker of If ) induced spontaneous discharge in quiescent SAN through ThVos . In spontaneous SAN, Cs+ increased Vos and 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 and inducing ThVos ; (ii) gradually accelerate SAN rate by predominantly increasing size and slope of earlier and more negative ThVos ; (iii) can induce sudden fast rhythms through the abrupt fusion of large Vos with large ThVos ; (iv) increase Vos and ThVos by increasing cellular calcium; and (v) do not modify the oscillatory potentials by means of the hyperpolarization-activated current If . The results provide evidence for novel mechanisms by which the SAN dominant pacemaker activity is initiated and enhanced by adrenergic agonists. [PUBLICATION ABSTRACT]