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-AC 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.