Reciprocal modulation of voltage-gated and background K(+) channels mediated by nucleotides and corticotropin

Bovine adrenal zona fasciculata (AZF) cells express two types of K(+)-selective ion channels including a rapidly inactivating bKv1.4 current (I(A)) and an ATP-dependent noninactivating background current (I(AC)) that sets the resting membrane potential. Whole-cell, patch-clamp recording from cultured AZF cells was used to demonstrate a novel reciprocal modulation of these two K(+) channels by intracellular nucleotides and corticotropin. Specifically, increases in I(AC) activity induced by intracellular ATP, as well as GTP and 5'-adenylyl-imidodiphosphate (AMP-PNP), were accompanied by a corresponding decrease in the amplitude of the voltage-gated I(A) current. The reduction in I(A) current was observed only when patch pipettes contained ATP or other nucleotides at concentrations sufficient to support activation of I(AC). Conversely, the nearly complete inhibition of I(AC) by corticotropin was accompanied by the coincident reappearance of functional I(A) channels. In the absence of I(AC) current, corticotropin failed to alter I(A). The reciprocal modulation of AZF cell K(+) channels by nucleotides and corticotropin was independent of membrane voltage. These results demonstrate a new form of channel modulation in which the activity of two different K(+) channels is reciprocally modulated in tandem through hormonal and metabolic signaling pathways. They further suggest that I(A) and I(AC) K(+) channels may be functionally coupled in a dynamic equilibrium driven by intracellular ATP and G-protein-coupled receptors. This may represent a unique mechanism for transducing biochemical signals to ionic events involved in cortisol secretion.