Intracellular Ca(2+)-Mediated Mechanisms for the Pacemaker Depolarization of the Mouse and Guinea Pig Sinus Node Tissue

Intracellular Ca(2+)-mediated mechanisms for pacemaker depolarization were studied in sinus node tissue preparations from mice and guinea pigs. Microelectrode recordings revealed that the sinus node of the mouse, which had a higher beating rate, had a steeper slope of the pacemaker depolarization than that of the guinea pig. BAPTA and ryanodine, agents that interfere with intracellular Ca(2+), significantly decreased the slope of the pacemaker depolarization in both species. In contrast, SEA0400, a specific inhibitor of the Na(+)-Ca(2+) exchanger (NCX), as well as change to low Na(+) extracellular solution, significantly decreased the slope in the mouse, but not in the guinea pig. Niflumic acid, a blocker of the Ca(2+) activated Cl(−) channel, decreased the slope in both species. Confocal microscopy revealed the presence of spontaneous Ca(2+) oscillations during the interval between Ca(2+) transients; such phenomenon was more pronounced in the mouse than in the guinea pig. Thus, although intracellular Ca(2+)-mediated mechanisms were involved in the pacemaker depolarization of the sinus node in both species, the NCX current was involved in the mouse but not in the guinea pig.