Inactivation of Delayed Potassium Current in Cultured Bovine Chromaffin Cells

Potassium currents of cultured bovine chromaffin cells in the presence of CdCl2 (0.5 mM) or CoCl2 (2 - 4 mM) may be described as a component that follows an n4 kinetics over the first 100 ms. However, during prolonged voltage clamp steps (5 - 20 s) this current reaches a peak and then declines to a non-zero steady-state level. In the absence of potassium accumulation, slow decay has been attributed to slow inactivation of the K+ conductance. Slow inactivation of calcium-independent potassium currents responds to the following: (i) the inactivation has a time course that may be fitted by a sum of two exponentials; (ii) inactivation is use-dependent (increasing frequency or duration of depolarizing pulses increases the extent of inactivation). Use-dependent inactivation does not appear when short (100 ms) hyperpolarizing prepulses are applied; (iii) at a membrane potential of - 60 mV, approximately 20% of the channels are inactivated; (iv) recovery from inactivation is very slow. At a holding potential of - 70 mV it takes about 20 s to reach the original value. The rate of inactivation recovery is voltage-dependent. The more hyperpolarized the membrane potential, the faster the recovery. The presence of use-dependent inactivation with slow recovery could be relevant for the stimulus - secretion coupling modulation in chromaffin cells.