We investigated the regulation of the Ca2+-activated K+ (maxi-K+) channel by angiotensin II (ANG II) and its synthetic analog, [Lys(2)]ANG II, in freshly dispersed intestinal myocytes. We identified a maxi-K+ channel population in the inside-out patch configuration on the basis of its conductance (257 +/- 4 pS in symmetrical 150 mM KCl solution), voltage and Ca2+ dependence of channel opening, low Na+-to-K+ and Cl--to-K+ permeability ratios, and blockade by external Cs+( )and tetraethylammonium chloride. ANG II and [Lys(2)]ANG II caused an indirect, reversible, Ca2+- and dose-dependent activation of maxi-K+ channels in cell-attached experiments when cells were bathed in high-K+ solution. This effect was reversibly blocked by DUP-753, being that it is mediated by the AT(1) receptor. Evidences that activation of the maxi-K+ channel by ANG II requires a rise in intracellular Ca2+ concentration ([Ca2+](i)) as an intermediate step were the shift of the open probability of the channel-membrane potential relationship to less positive membrane potentials and the sustained increase in [Ca2+](i) in fura 2-loaded myocytes. The preservation of the pharmacomechanical coupling of ANG II in these cells provides a good model for the study of transmembrane signaling responses to ANG II and analogs in this tissue.
