In the heart, the frequency of spontaneous electrical activity generated in the sinoatrial node (SAN) is determined by diastolic depolarization which is believed to be formed by ion channel-dependent membrane potential changes. It has also been proposed that intracellular Ca²⁺ may regulate spontaneous activity via electrogenic Na⁺/Ca²⁺ exchanger (NCX); Ca²⁺ clock theory. In this study, we investigated whether NCX contributes to spontaneous activity in guinea pig SAN.
Immunofluorescence staining showed the expression of NCX on the cell membrane of the SAN cells.
To evaluate the role of NCX in spontaneous activity and Ca²⁺ dynamics, high-speed Ca²⁺ imaging was performed on SAN cells and spontaneous Ca²⁺ transients were observed. The inhibition of NCX activity by perfusion with low Na⁺ solution resulted in an increase in the basal fluorescence intensity, but had little effect on the frequency of Ca²⁺ transients. Glass microelectrode recording of action potential revealed that low Na⁺ solution has no effect on the diastolic depolarization. Furthermore, SEA0400, an inhibitor of NCX, did not affect the frequency of spontaneous activity and the diastolic depolarization.
These results suggest that, although NCX is expressed in guinea pig SAN cells and is responsible for Ca²⁺ efflux, its contribution to spontaneous activity is very small.