Selective inhibition of potassium-stimulated rat adrenal glomerulosa cells by ruthenium red.
The effect of the cationic dye, ruthenium red (RR), on ionic fluxes, Ca2+ signal generation, and stimulation of aldosterone production was studied in isolated rat adrenal glomerulosa cells. In these cells, increased extracellular [K+] as well as angiotensin II (Ang II) elevate cytoplasmic Ca2+ concentration and thereupon activate steroidogenesis. However, the mode of action of the two stimuli are different: while a dihidropyridine-sensitive mechanism contributes to the response to both agonists, Ang II induces Ca2+ release from intracellular stores and causes capacitative Ca2+ influx, whereas K+ was recently shown to activate a plasma membrane Ca2+ current (Igl) independently of membrane depolarization. The difference is reflected in the sensitivity of the response of the cells to RR. The Ang II-induced Ca2+ signal and aldosterone production were not inhibited, but rather slightly potentiated by the dye. This potentiation was probably the consequence of the membrane-depolarizing effect of RR, due to the observed inhibition of the resting K+ conductance. Conversely, Ca2+ signal and aldosterone production were significantly reduced by RR when the cells were stimulated by moderately elevated [K+] (6-8 mM). Our patch clamp studies suggest that this effect was related to the inhibition of different voltage-dependent and -independent inward Ca2+ currents and indicates the functional importance of the latter in the signal transduction of the potassium-stimulated glomerulosa cell.
Szabadkai
G
G
Department of Physiology, Semmelweis University of Medicine, Budapest, Hungary.
Várnai
P
P
Enyedi
P
P
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D004396:Coloring Agents; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000037:antagonists & inhibitors*; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology*; D013268:Stimulation, Chemical; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects*
D015220:Calcium Channels; D004396:Coloring Agents; D026902:Potassium Channel Blockers; D012430:Ruthenium Red; D000804:Angiotensin II; D011188:Potassium