Hypoxia-induced catecholamine release and intracellular Ca2+ increase via suppression of K+ channels in cultured rat adrenal chromaffin cells.
Hypoxia (5% O2) enhanced catecholamine release in cultured rat adrenal chromaffin cells. Also, the intracellular free Ca2+ concentration ([Ca2+]i) increased within 3 min in approximately 50% of the chromaffin cells under hypoxic stimulation. The increase depended on the presence of extracellular Ca2+. Nifedipine and omega-conotoxin decreased the population of the cells that showed the hypoxia-induced [Ca2+]i increase, showing that the Ca2+ influx was attributable to L- and N-type voltage-dependent Ca2+ channels. The membrane potential was depolarized during the perfusion with the hypoxic solution and returned to the basal level following the change to the normoxic solution (20% O2). Membrane resistance increased twofold under the hypoxic condition. The current-voltage relationship showed a hypoxia-induced decrease in the outward K+ current. Among the K+ channel openers tested, cromakalim and levcromakalim, both of which interact with ATP-sensitive K+ channels, inhibited the hypoxia-induced [Ca2+]i increase and catecholamine release. The inhibitory effects of cromakalim and levcromakalim were reversed by glibenclamide and tolbutamide, potent blockers of ATP-sensitive K+ channels. These results suggest that some fractions of adrenal chromaffin cells are reactive to hypoxia and that K+ channels sensitive to cromakalim and glibenclamide might have a crucial role in hypoxia-induced responses. Adrenal chromaffin cells could thus be a useful model for the study of oxygen-sensing mechanisms.
Mochizuki-Oda
N
N
International Institute for Advanced Research, Central Research Laboratory, Matsushita Electric Industrial Co., Ltd., Kyoto, Japan.
Takeuchi
Y
Y
Matsumura
K
K
Oosawa
Y
Y
Watanabe
Y
Y
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002021:Buffers; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002344:Carotid Body / Q000737:chemistry / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D019439:Chromaffin Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D006224:Cricetinae; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology; D005910:Glioma; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006822:Hybrid Cells; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008914:Minoxidil / Q000494:pharmacology; D009447:Neuroblastoma; D010276:Parasympatholytics / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D002021:Buffers; D002395:Catecholamines; D006146:Guanidines; D007004:Hypoglycemic Agents; D010276:Parasympatholytics; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D008914:Minoxidil; D020110:Pinacidil; D003981:Diazoxide; D011188:Potassium; D005905:Glyburide; D002118:Calcium