In general, smaller animals have higher heart rates, suggesting that there are differences in the mechanisms of pacemaker depolarization. Recently, it has been postulated that the pacemaker depolarization is influenced by intracellular Ca²⁺. This study intended to clarify the intracellular Ca²⁺-mediated mechanisms involved in the pacemaker depolarization of the mouse and guinea pig sinus node.
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. Intracellular Ca²⁺ interfering agents, BAPTA and ryanodine, significantly decreased the slope in both species. In contrast, SEA0400, a specific inhibitor of the Na⁺-Ca²⁺ exchanger (NCX), as well as change to low Na⁺ extracellular solution, significantly decreased the slope in the mouse, but not in the guinea pig. Confocal microscopy revealed the presence of spontaneous Ca²⁺ oscillations during the interval between Ca²⁺ transients; Ca²⁺ oscillations were more pronounced in the mouse than in the guinea pig.
These results suggested that, although intracellular Ca²⁺-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.