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

1. The Na+-dependent inward currents underlying slow diastolic depolarizati on of sinoatrial (SA) node cells mere examined. Using a Na+-rich, Ca2+-free pipette solution a novel single channel current was recorded in addition t o the conventional Naf and L-type Ca2+ currents. The current (termed i(st), as it reflects the whole-cell sustained inward current, I-st) does not sho w obvious inactivation during a 700 ms depolarization and is unique in havi ng a smaller amplitude (1.1 +/- 0.18 pA at -60 mV, n = 12) than the Na+ cur rent through conventional Na+ (similar to 3.3 pA) and Ca2+ channels (9.6 +/ - 0.32 pA at -60 mV, n = 8). The mean unitary conductance of i(st) channels was 13.3 pS. 2. The recording of i(st) was infrequent, was observed only in spontaneousl y beating BA node cells, and was facilitated by adding Bay-K 8644 to the pi pette solution. Overlapping of i(st) events was observed and i(st) was abol ished by bath application of nicardipine. 3. In the ensemble average, the activation of i(st) was evident by depolari zation beyond -70 mV, and the dynamic voltage range of activation (-70 to - 30 mV) encompassed the extent of the slow diastolic depolarization. The cur rent density of i(st) was 0.33 pA pF(-1) at -60 mV, as estimated from the n umber 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 d epolarization, while the fast time constants and the fraction of the fast c omponent 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+ chan nels and decreased with depolarization. 5. It is suggested that the i(st) channels might be responsible for the who le-cell I-st.