title: The role of dihydropyridine-sensitive Ca2+ channels in stimulus-evoked catecholamine release from chemoreceptor cells of the carotid body.
abstract: The present study utilized an in vitro preparation of the rabbit carotid body, with tissue catecholamine stores labeled by incubation with 3H-tyrosine. The goal was to characterize pharmacologically the voltage-dependent Ca2+ channels present in the type I (glomus) cells of this arterial chemoreceptor organ, and to elucidate their role as pathways for Ca2+ entry. We found that release of 3H-dopamine induced by high external potassium was over 95% dependent on external calcium concentration and that this release was 90-100% inhibited by the dihydropyridine antagonists, nisoldipine and nitrendipine, and was potentiated by the dihydropyridine agonist, BayK 8644. Therefore, any stimulus-induced, calcium-dependent release of 3H-dopamine that was inhibited by nisoldipine and potentiated by BayK 8644, was considered to be supported by Ca2+ entry into the cells via voltage-dependent Ca2+ channels. Significant differences were observed in the release of 3H-dopamine induced by 75 vs 25 mM K+. On prolonged stimulation, release induced by 75 mM K+ was large and transient, whilst that induced by 25 mM K+, although more moderate, was sustained. The release elicited by 75 mM K+ was inhibited approximately 90% by 1.5 mM Co2+ or 625 nM nisoldipine, while release by 25 mM K+ was completely blocked by 0.6 mM Co2+ or 125 nM nisoldipine. Low PO2-induced release of 3H-dopamine was 95% dependent on Ca2+, and was inhibited by nisoldipine (625 nM) in a manner inversely proportional to the intensity of hypoxic stimulation, i.e. 79% inhibition at a PO2 of 49 Torr, and 20% inhibition at PO2 of 0 Torr. BayK 8644 potentiated the release induced by moderate hypoxic stimuli. Release elicited by high PCO2/low pH, or by Na(+)-propionate or dinitrophenol-containing solutions, was approximately 80% Ca(2+)-dependent, and the dihydropyridines failed to modify this release. It is concluded that type I cells possess voltage-dependent Ca2+ channels sensitive to the dihydropyridines, which in agreement with previous electrophysiological data should be defined as L-type Ca2+ channels. Calcium entry which supports the release of 3H-dopamine elicited by moderate hypoxia should occur mainly through these channels while the release induced by strong hypoxic stimuli will be served by Ca2+ entry which occurs in part via voltage-dependent Ca2+ channels, and in part through an additional pathway, probably a Na+/Ca2+ exchanger.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology, University of Utah School of Medicine, Salt Lake City 84108.
authors.forename: A
authors.initials: A
authors.lastname: Obeso
authors.forename: A
authors.initials: A
authors.lastname: Rocher
authors.forename: S
authors.initials: S
authors.lastname: Fidone
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002132:Calcium Radioisotopes; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D002395:Catecholamines; D004095:Dihydropyridines; D011188:Potassium; D004298:Dopamine