Vol. 60, Issue 1, 114-123, July 2001

Reciprocal Modulation of Voltage-Gated and Background K⁺ Channels Mediated by Nucleotides and Corticotropin

John J. Enyeart, Lin Xu, Juan Carlos Gomora, and Judith A. Enyeart

Department of Neuroscience, The Ohio State University, College of Medicine, Columbus, Ohio

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.