Spontaneous frequency of rabbit atrioventricular node myocytes depends on SR function

Spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) appears to play an important role in cardiac sinoatrial node pacemaking. However, comparatively little is known about the role of intracellular Ca2+ in the atrioventricular node (AVN). Intracellular Ca2+ was therefore monitored in cells isolated from the rabbit AVN, using fluo-3 in conjunction with confocal microscopy. These cells displayed spontaneous Ca2+ transients and action potentials. Ca2+ transients were normally preceded by a small, slow increase (ramp) of intracellular Ca2+ which was sometimes, but not always, accompanied by Ca2+ sparks. During the Ca2+ transient, intracellular [Ca2+] increased initially at the cell periphery and propagated inhomogeneously to the cell centre. The rate of spontaneous activity was decreased by ryanodine (1 μM) and increased by isoprenaline (500 nM); these changes were accompanied by a decrease and increase, respectively, in the slope of the preceding Ca2+ ramp, with no significant change in Ca2+ spark characteristics. Rapidly reducing bathing [Na+] inhibited spontaneous activity. These findings provide the first information on Ca2+ handling at the sub-cellular level and link cellular Ca2+ cycling to the genesis of spontaneous activity in the AVN.