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 V(os) and ThV(os). As high [K(+)](o) perfusion continues, the oscillatory potentials become separated, V(os) following the AP and ThV(os) appearing later on, when DD enters a less negative voltage range (oscillatory zone). ThV(os) grow in amplitude and attain the threshold, thereby insuring a slow discharge. If [K(+)](o) is further increased, the smaller ThV(os) miss the threshold and SA node becomes quiescent. On reducing high [K(+)](o), ThV(os) re-appear, increase in size and initiate spontaneous discharge. As they occur progressively earlier during DD, ThV(os) eventually fuse with V(os): 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 V(os) and of ThV(os) 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 [Ca(2+)](o) or applying a fast drive increase the size and slope of V(os) and of ThV(os), which in turn restore or accelerate discharge. In contrast, low [Ca(2+)](o) abolishes V(os) and ThV(os) and causes SA node arrest. Low [Ni(2+)] (35.5 microM) increases the rate whereas high [Ni(2+)] (0.73 mM) stops the SA node. Ryanodine eliminates V(os) and ThV(os) and markedly slows or stops discharge. Thus, ThV(os) and V(os) are separate voltage oscillations that play an obligatory role in the initiation and maintenance of SA node discharge, V(os) by steepening early DD and ThV(os) by attaining the threshold in the dominant pacemaker range, either by gradually increasing during late DD at slow rates or by fusing with V(os) at fast rates. Both V(os) and ThV(os) are Ca(2+) dependent, but apparently in different ways.