HYPOXIA-INDUCED CATECHOLAMINE RELEASE AND INTRACELLULAR CA2+ INCREASEVIA SUPPRESSION OF K+ CHANNELS IN CULTURED RAT ADRENAL CHROMAFFIN CELLS

Hypoxia (5% O-2) enhanced catecholamine release in cultured rat adrena l chromaffin cells, Also, the intracellular free Ca2+ concentration ([ Ca2+](i)) increased within 3 min in similar to 50% of the chromaffin c ells under hypoxic stimulation, The increase depended on the presence of extracellular Ca2+. Nifedipine and omega-conotoxin decreased the po pulation of the cells that showed the hypoxia-induced [Ca2+](i) increa se, showing that the Ca2+ influx was attributable to L- and N-type vol tage-dependent Ca2+ channels, The membrane potential was depolarized d uring-the perfusion with the hypoxic solution and returned to the basa l level following the change to the normoxic solution (20% O-2) Membra ne resistance increased two-fold under the hypoxic condition. The curr ent-voltage relationship showed a hypoxia-induced decrease in the outw ard KC current, Among the KC channel openers tested, cromakalim and le vcromakalim, both of which interact with ATP-sensitive K+ channels, in hibited the hypoxia-induced [Ca2+](i) increase and catecholamine relea se. The inhibitory effects of cromakalim and levcromakalim were revers ed by glibenclamide and tolbutamide, potent blockers of ATP-sensitive K+ channels. These results suggest that some fractions of adrenal chro maffin cells are reactive to hypoxia and that K+ channels sensitive to cromakalim and glibenclamide might have a crucial role in hypoxia-ind uced responses. Adrenal chromaffin cells could thus be a useful model for the study of oxygen-sensing mechanisms.