Modulation of a Ca(2+)-activated K+ channel by angiotensin II in rat adrenal glomerulosa cells: involvement of a G protein.
In the present study, we demonstrate the presence of Ca(2+)-activated K+ channels in rat glomerulosa cells. We find that angiotensin II (Ang II) inhibits this charybdotoxin-sensitive current. The effect of Ang II was dose-dependent with an inhibition constant (Ki) of 0.98 nM and a maximal effect observed at 200 nM. Time course of the blockage was as rapid as the one induced by charybdotoxin. This effect is mediated by the AT1 receptor subtype of Ang II, since it is blocked by DUP 753 but is unaffected by CGP 42112. Activation of protein kinase C by phorbol dibutyrate (1 microM) or dialysis of the cell with inositol 1,4,5-triphosphate (20 microM) were ineffective in blocking the current. However, experiments done with GDP beta S and GTP gamma S indicated that a G protein was involved. The inhibitory effect of Ang II was not pertussis toxin-sensitive, which excludes Gi protein, but was abrogated if an antibody raised against the alpha-subunit of the Gq/11 protein was present in the patch pipette medium. Further analysis showed that the Ca(2+)-activated K+ channel was able to modulate the membrane potential according to the level of intracellular calcium concentration ([Ca2+]i). Whereas a thapsigargin-induced increase in [Ca2+]i hyperpolarized the membrane, this effect was not observed when Ang II was used to increase [Ca2+]i because of the blockage of the Ca(2+)-activated K+ current. The blockage of Ca(2+)-activated K+ current by Ang II would result in a synergistic effect on the Ang II-induced depolarization, thus favoring Ca2+ influx, an event essential to secretion.
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D015640:Ion Channel Gating; D008564:Membrane Potentials; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000502:physiology; D015384:Zona Glomerulosa / Q000502:physiology*
D015221:Potassium Channels; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium