Evolution of the Ca2+ current during dialysis of isolated bovine chromaffin cells: effect of internal calcium.

We have examined the internal Ca(2+)-dependence of the long-term evolution of whole cell high voltage activated Ca current in chromaffin cells. The evolution of the peak Ca current was characterized by 2 distinct phases: after an initial facilitation, there followed a rundown, which represented a reduction by 70% within some 10 min. The rundown process was shown not to depend on Ca2+ entry nor on membrane depolarization. It resulted from cell dialysis with a saline solution and, once initiated, it proceeded at a rate of 0.28 min-1 at 4 different Ca2+ concentrations (pCa 5-9). The facilitation is also initiated by cell dialysis but this process developed faster at higher internal Ca2+ concentrations. Thus, globally, high-voltage activated Ca2+ current runs down faster when using a recording pipette solution with a higher internal Ca2+ concentration (pCa 5 or 6). Some leupeptin-sensitive proteases may be involved in the initiation of facilitation and rundown processes.