Obligatory role of diastolic voltage oscillations in sino-atrial node discharge

The role of diastolic voltage oscillations in the initiation and maintenance of pacemaker discharge was studied in guinea pig-isolated sino-atrial (SA) node by means of a microelecrode technique. When [K+]o is suitably increased, the maximum diastolic potential decreases and all action potentials (APs) assume the characteristics of dominant pacemakers (slow responses with U-shaped diastolic depolarization). Subsequently, as the slope and amplitude of diastolic depolarization (DD) decreases, the threshold is missed, unmasking the fused oscillatory potentials Vos and ThVos. As high [K+]o perfusion continues, the oscillatory potentials become separated, Vos following the AP and ThVos appearing later on, when DD enters a less negative voltage range (oscillatory zone). ThVos grow in amplitude and attain the threshold, thereby insuring a slow discharge. If [K+]o is further increased, the smaller ThVos miss the threshold and SA node becomes quiescent. On reducing high [K+]o, ThVos re-appear, increase in size and initiate spontaneous discharge. As they occur progressively earlier during DD, ThVos eventually fuse with Vos: at that stage, DD appears to continue directly into the upstroke (U-shaped DD) and the oscillations are no longer seen. During recovery in Tyrode solution, size and slope of Vos and of ThVos further increase and cause a faster discharge. When APs assume a subsidiary configuration, their DD (no longer U-shaped) abruptly terminates into the upstroke. In high [K+]o, increasing [Ca2+]o or applying a fast drive increase the size and slope of Vos and of ThVos, which in turn restore or accelerate discharge. In contrast, low [Ca2+]o abolishes Vos and ThVos and causes SA node arrest. Low [Ni2+] (35.5 μM) increases the rate whereas high [Ni2+] (0.73 mM) stops the SA node. Ryanodine eliminates Vos and ThVos and markedly slows or stops discharge. Thus, ThVos and Vos are separate voltage oscillations that play an obligatory role in the initiation and maintenance of SA node discharge, Vos by steepening early DD and ThVos by attaining the threshold in the dominant pacemaker range, either by gradually increasing during late DD at slow rates or by fusing with Vos at fast rates. Both Vos and ThVos are Ca2+ dependent, but apparently in different ways.