Selective inhibition of potassium-stimulated rat adrenal glomerulosa cellsby ruthenium red

The effect of the cationic dye, ruthenium red (RR), on ionic fluxes, Ca2+ s ignal generation, and stimulation of aldosterone production was studied in isolated rat adrenal glomerulosa cells. In these cells, increased extracell ular [K+] as well as angiotensin II (Ang II) elevate cytoplasmic Ca2+ conce ntration and thereupon activate steroidogenesis. However, the mode of actio n of the two stimuli are different: while a dihidropyridine-sensitive mecha nism contributes to the response to both agonists, Ang II induces Ca2+ rele ase from intracellular stores and causes capacitative Ca2+ influx, whereas K+ was recently shown to activate a plasma membrane Ca2+ current (I-gl) ind ependently of membrane depolarization. The difference is reflected in the s ensitivity of the response of the cells to RR. The Ang II-induced Ca2+ sign al and aldosterone production were not inhibited, but rather slightly poten tiated by the dye. This potentiation was probably the consequence of the me mbrane depolarizing effect of RR, due to the observed inhibition of the res ting K+ conductance. Conversely, Ca2+ signal and aldosterone production wer e significantly reduced by RR when the cells were stimulated by moderately elevated [K+] (6-8 mM). Our patch clamp studies suggest that this effect wa s 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. B IOCHEM PHARMACOL 57;2:209-218, 1999. (C) 1998 Elsevier Science Inc.