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

Autor: Michael P. Nett, Mario Vassalle
Rok vydání: 2003
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology. 35:1257-1276
ISSN: 0022-2828
Popis: 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 μM) 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.
Databáze: OpenAIRE