Voltage-gated Na⁺ channels are the primary molecules responsible for the rising phase of the action potential in electronically excitable cells. The majority of Na⁺ channels in the heart are cardiac-type Na⁺ channels, but brain-type Na⁺ channels have also been recently identified in murine heart including sinoatrial node (SAN) (Maier et al. 2002), but the role of brain type Na⁺ channels in SAN has not been clarified. In this study, we have isolated and characterized a TTX-sensitive Na⁺ current from murine SAN pacemaker cells and examined its role in murine SAN pacemaking.

Hearts were excised from 20-25 g adult C57BL mice humanely killed by cervical dislocation. Single SAN cells were isolated as we described previously (Lei et al. 2002a). TTX (100 nM) was used to dissect out sodium channel subtypes from total sodium current. Nifedipine (300 nM) was applied to block I_Ca,L. External sodium concentration was decreased to 70 mM (replaced by CsCl).

Extracellular potentials (ECPs) were recorded as we described previously (Lei et al. 2002b). A TTX-sensitive inward current was recorded by 20 ms depolarising step pulses from a holding potential of -120 mV to various test potentials between -90 and +40 mV. At body temperature, the current starts to activate at -60 mV and peaks at -10 mV with a current density of -21.8 ± 2 pA pF^-1 (n = 6). Block of brain-type Na⁺ channels by 100 nM TTX decreases spontaneous beating rate in both intact SAN and isolated pacemaker cells. Figure 1 shows an example of continuous recording of the effect of 100 nM TTX on the leading pacemaker site.

The results suggest that brain-type Na⁺ current contributes to murine cardiac pacemaking.

This work was supported by The Wellcome Trust.