Abstract

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.