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 (I-gl) 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. BIOCHEM PHARMACOL 57;2:209-218, 1999. (C) 1998 Elsevier Science Inc.