Intracellular Ca-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, significantly decreased the slope of the pacemaker depolarization in both species. In contrast, SEA0400, a specific inhibitor of the Na-Ca 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 activated Cl channel, decreased the slope in both species. Confocal microscopy revealed the presence of spontaneous Ca oscillations during the interval between Ca transients; such phenomenon was more pronounced in the mouse than in the guinea pig. Thus, although intracellular Ca-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.
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