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

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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)

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