Ryanodine- and thapsigargin-insensitive Ca2+-induced Ca2+ release is primed by lowering external Ca2+ in rabbit autonomic neurons

Rises in cytosolic Ca2+ induced by a high K+ concentration (30 or 60 mM) (K +-induced Ca2+ transient) were recorded by fluorimetry of Ca2+ indicators i n cultured rabbit otic ganglion cells. When external Ca2+ ([Ca2+](o)) was r educed to a micromolar (10-40 mu M) or nanomolar (<10 nM) level prior to hi gh-K+ treatment, K+-induced Ca2+ transients of considerable amplitude (50% of control) were generated in most cells, although those initiated at norma l [Ca2+], were reduced markedly or abolished by reducing [Ca2+](o) during e xposure to a high K+ concentration. Lowering [Ca2+](o) alone occasionally c aused a transient rise in cytosolic Ca2+. K+-induced Ca2+ transients at mic romolar [Ca2+](o) were repeatedly generated and propagated inwardly at a sp eed slower than that at normal [Ca2+](o), while those at nanomolar [Ca2+](o ) occurred only once. K+-induced Ca2+ transients at micromolar [Ca2+](o) we re not blocked by ryanodine (10 mu M), carbonyl cyanide p-(triflnoromethoxy ) phenyl-hydrazone (FCCP, 5 mu M: at 20-22 degrees C but blocked at 31-34 d egrees C) or thapsigargin (1-2 mu M), but were blocked by Ni2+(1 mM) or nic ardipine (10 mu M). Thus, there is a ryanodine-insensitive Ca2+-release mec hanism in FCCP-and thapsigargin-insensitive Ca2+ stores in rabbit otic gang lion cells, which is primed by lowering [Ca2+](o) and then activated by dep olarization-induced Ca2+ entry. This Ca2+-induced Ca2+ release may operate when [Ca2+](o) is decreased by intense neuronal activity.