OUTWARD POTASSIUM CURRENT OSCILLATIONS IN MACROPHAGE POLYKARYONS - EXTRACELLULAR CALCIUM-ENTRY AND CALCIUM-INDUCED CALCIUM-RELEASE

Outward current oscillations associated with transient membrane hyperp olarizations were induced in murine macrophage polykaryons by membrane depolarization in the absence of external Na+. Oscillations correspon ded to a cyclic activation of Ca2+-dependent K+ currents (IKCa) probab ly correlated with variations in intracellular Ca2+ concentration. Add ition of external Na+ (8 mM) immediately abolished the outward current oscillations, suggesting that the absence of the cation is necessary not only for their induction but also for their maintenance. Oscillati ons were completely blocked by nisoldipine. Ruthenium red and ryanodin e reduced the number of outward current cycles in each episode, wherea s quercetin prolonged the hyperpolarization 2- to 15-fold. Neither low molecular weight heparin nor the absence of a Na+ gradient across the membrane had any influence on oscillations. The evidence suggests tha t Ca2+ entry through a pathway sensitive to Ca2+ channel blockers is e licited by membrane depolarization in Na+-free medium and is essential to initiate oscillations, which are also dependent on the cyclic rele ase of Ca2+ from intracellular Ca2+-sensitive stores; Ca2+ ATPase acts by reducing intracellular Ca2+, thus allowing slow deactivation of IK Ca. Evidence is presented that neither a Na+/Ca2+ antiporter nor Ca2release from IP3-sensitive Ca2+ stores participate directly in the mec hanism of oscillation.