Activation of Ca2+-activated K+ (maxi-K+) channel by angiotensin II in myocytes of the guinea pig ileum

We investigatedthe regulation of theCa²⁺-activatedK⁺(maxi-K⁺) channel by angiotensinII (ANG II) and its synthetic analog, Lys²]ANG II, infreshly dispersed intestinal myocytes. We identified amaxi-K⁺ channel population in theinside-out patch configuration on the basis of its conductance (257 ± 4 pS in symmetrical 150 mM KCl solution), voltage andCa²⁺ dependence of channelopening, lowNa⁺-to-K⁺andCl-to-K⁺permeability ratios, and blockade by externalCs⁺ and tetraethylammoniumchloride. ANG II andLys²]ANG II caused anindirect, reversible, Ca²⁺- anddose-dependent activation ofmaxi-K⁺ channels in cell-attachedexperiments when cells were bathed inhigh-K⁺ solution. This effect wasreversibly blocked by DUP-753, being that it is mediated by theAT₁ receptor.Evidences that activation of themaxi-K⁺ channel by ANG II requiresa rise in intracellular Ca²⁺concentration(Ca²⁺]_i)as an intermediate step were the shift of the open probability of thechannel-membrane potential relationship to less positive membranepotentials and the sustained increase inCa²⁺]_iin fura 2-loaded myocytes. The preservation of the pharmacomechanical coupling of ANG II in these cells provides a good model for the studyof transmembrane signaling responses to ANG II and analogs in thistissue.