Na(+)‐Ca2+ exchange current in latent pacemaker cells isolated from cat right atrium.

1. Single latent pacemaker cells were isolated from cat right atrium, and studied in a whole‐cell configuration using a nystatin‐perforated patch recording method. The nystatin method avoids alterations in intracellular Ca2+, cellular constituents and run‐down of ionic currents. 2. Depolarizing voltage clamp pulses from ‐40 mV elicited L‐type Ca2+ current (ICa) that exhibited an initial rapid phase of inactivation followed by a secondary slower inward current component that decayed over about 100 ms. The secondary inward component appeared as a slowly decaying inward tail current following short (10‐40 ms) depolarizing clamp steps. 3. Slowly decaying inward currents were abolished by internally dialysing pacemaker cells with 2 mM EGTA using a ruptured patch recording method. Inward tail currents were also abolished by exposure to 1 microM ryanodine and significantly decreased by replacing 85% of external Na+ with lithium, without effect on peak ICa. These findings identify a Na(+)‐Ca2+ exchange current (INa‐Ca) that is mediated by sarcoplasmic reticulum (SR) Ca2+ release. 4. Properties of INa‐Ca and ICa differed significantly: (i) ICa exhibited a bell‐shaped voltage dependence that peaked at 0 mV and decreased at more positive voltages. INa‐Ca was maximal at ‐10 mV and remained relatively constant at more positive voltages; (ii) a paired pulse protocol showed that the time course of INa‐Ca recovery (5 s) was significantly longer than that of ICa (2 s); (iii) cadmium (50 microM) induced an inhibition of ICa that did not correlate in time with changes in INa‐Ca. 5. The duration of depolarizing steps between 10 and 120 ms had no effect on the time course of INa‐Ca tail currents. 6. Isoprenaline > or = 5 x 10(‐8) M significantly increased peak ICa amplitude, peak INa‐Ca amplitude, accelerated INa‐Ca rate of decay and decreased the absolute time of INa‐Ca decay. 7. Free‐running pacemaker action potentials were clamped during diastole at either ‐40 or ‐70 mV (maximum diastolic potential) for variable periods of time. At times between 0.2 and 1 s, INa‐Ca exhibited a voltage‐dependent increase in amplitude over time, i.e. INa‐Ca recovered more rapidly from ‐70 mV than from ‐40 mV. At times > 2 s, INa‐Ca exhibited a voltage‐dependent decline in amplitude over time, i.e. from ‐40 mV INa‐Ca decreased by 10% of maximum whereas from ‐70 mV INa‐Ca decreased by 60% of maximum.(ABSTRACT TRUNCATED AT 400 WORDS)