Pyridine nucleotide redox state parallels production of aldosterone in potassium-stimulated adrenal glomerulosa cells.
Extracellular potassium ions (K+) raise the intracellular concentration of free Ca2+ ([Ca2+]i) by gating voltage-dependent Ca2+ channels and stimulate aldosterone production in adrenal glomerulosa cells. The pathway leading from calcium influx to increased steroid synthesis has not been completely elucidated. In the present study we demonstrate that the reduction of pyridine nucleotides known to be required for steroid hydroxylation is enhanced by K+ (4.1-8.4 mM) in single rat glomerulosa cells. The action of K+ was strictly dependent on the presence of extracellular Ca2+. Amytal, a blocker of site I of the mitochondrial respiratory chain, abolished the K+ effect, indicating a mitochondrial origin for the recorded changes. Supraphysiological K+ concentration (18 mM) resulted in a further increase in [Ca2+]i, while steroidogenesis was decreased as measured in cell suspensions. However, a possible explanation for this dichotomy is provided by the finding that the level of reduced pyridine nucleotides also decreased at supraphysiological K+ concentration.
Pralong
W F
WF
Department of Medicine, University of Geneva, Switzerland.
Hunyady
L
L
Várnai
P
P
Wollheim
C B
CB
Spät
A
A
D000450:Aldosterone / Q000096:biosynthesis*; D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D015384:Zona Glomerulosa / Q000378:metabolism*
D009243:NAD; D000450:Aldosterone; D009249:NADP; D000654:Amobarbital; D011188:Potassium; D002118:Calcium