Nicardipine‐sensitive Na+‐mediated single channel currents in guinea‐pig sinoatrial node pacemaker cells

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Abstract
1. The Na+-dependent inward currents underlying slow diastolic depolarization of sinoatrial (SA) node cells were examined. Using a Na+-rich, Ca2+-free pipette solution a novel single channel current was recorded in addition to the conventional Na+ and L-type Ca2+ currents. The current (termed ist, as it reflects the whole-cell sustained inward current, Ist) does not show obvious inactivation during a 700 ms depolarization and is unique in having a smaller amplitude (1.1 +/- 0.18 pA at -60 mV, n = 12) than the Na+ current through conventional Na+ ( approximately 3.3 pA) and Ca2+ channels (9.6 +/- 0.32 pA at -60 mV, n = 8). The mean unitary conductance of ist channels was 13.3 pS. 2. The recording of ist was infrequent, was observed only in spontaneously beating SA node cells, and was facilitated by adding Bay-K 8644 to the pipette solution. Overlapping of ist events was observed and ist was abolished by bath application of nicardipine. 3. In the ensemble average, the activation of ist was evident by depolarization beyond -70 mV, and the dynamic voltage range of activation (-70 to -30 mV) encompassed the extent of the slow diastolic depolarization. The current density of ist was 0.33 pA pF-1 at -60 mV, as estimated from the number of channels per membrane patch, the open probability and the unitary amplitude. 4. Cumulative histograms for both open and closed times were fitted with a sum of two exponential components. The slow time constants decreased with depolarization, while the fast time constants and the fraction of the fast component were voltage independent. The number of bursts per sweep increased with depolarization. The time constant of the first latency histogram was about two orders of magnitude larger than those in cardiac L-type Ca2+ channels and decreased with depolarization. 5. It is suggested that the ist channels might be responsible for the whole-cell Ist.