The low-affinity dihydropyridine receptor and Na+/Ca2+ exchanger are associated in adrenal medullary mitochondria

• Published in: Biochemical pharmacology Vol. 50; no. 6; pp. 879 - 883
• Main Authors: PALMERO, M, GUTIERREZ, L. M, HIDALGO, M. J, REIG, J. A, BALLESTA, J. J, VINIEGRA, S
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 07.09.1995
• Subjects: Adrenal Medulla - metabolism; Animals; Antihypertensive agents; Binding Sites; Biological and medical sciences; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; Calcium Channels, L-Type; Cardiovascular system; Carrier Proteins - metabolism; Cattle; Medical sciences; Mitochondria - metabolism; Nitrendipine - metabolism; Pharmacology. Drug treatments; Sodium - metabolism; Sodium-Calcium Exchanger; Vertebrata; Mitochondria; Mammalia; Bovine; Animal; Adrenal medulla; Calcium antagonist; Artiodactyla; In vitro; Ungulata; Dihydropyridine derivative; Biological receptor
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(95)00194-5

The effect of Ca2+ channel-acting drugs on bovine adrenal mitochondria Ca2+ movements was investigated. Mitochondrial Ca2+ uptake is performed by an energy-driven Ca2+ uniporter with a Km of 20.9 +/- 3.2 microM and Vmax of 148.1 +/- 7.2 nmol 45Ca2+ min-1 mg-1. Ca2+ release is performed through an Na+/Ca2+ antiporter with a Km for Na+ of 4.2 +/- 0.5 mM, a Vmax of 7.5 +/- 0.4 nmol 45Ca2+ min-1 mg-1, and a Hill coefficient of 1.4 +/- 0.2 Ca2+ efflux through the mitochondrial Na+/Ca2+ exchanger was inhibited by several dihydropyridines (nitrendipine, felodipine, nimodipine, (+)isradipine) and by the benzothiazepine diltiazem with similar potencies. In contrast, neither CGP 28392, Bay-K-8644, amlodipine, nor verapamil had any effect on Ca2+ efflux. Nitrendipine at 20 microM modified neither the Km nor the Hill coefficient for Na+, whereas the Vmax was reduced to 2.9 nmol 45Ca2+ min-1 mg-1, thus demonstrating noncompetitive modulation of the Na+/Ca2+ exchanger. None of the Ca2+ channel-acting drugs assayed at 100 microM affected Ca2+ influx through the uniporter. Ca2+ channel blockers inhibited the Na+/Ca2+ antiporter and displaced the specific binding of [3H]nitrendipine to intact mitochondria with Ki values similar to the IC50s obtained for the inhibition of the Ca2+ efflux. Ca2+ channel-acting drugs that did not inhibit the Na+/Ca2+ exchanger (amlodipine, CGP 28392, Bay-K-9644, and verapamil, at concentrations of 100 microM or higher) had no effect on [3H]nitrendipine binding. These results suggest that the adrenomedullary mitochondrial dihydropyridine receptor is associated with the Na+/Ca2+ exchanger.