PT - JOURNAL ARTICLE AU - John J. Enyeart AU - Lin Xu AU - Juan Carlos Gomora AU - Judith A. Enyeart TI - Reciprocal Modulation of Voltage-Gated and Background K<sup>+</sup> Channels Mediated by Nucleotides and Corticotropin AID - 10.1124/mol.60.1.114 DP - 2001 Jul 01 TA - Molecular Pharmacology PG - 114--123 VI - 60 IP - 1 4099 - http://molpharm.aspetjournals.org/content/60/1/114.short 4100 - http://molpharm.aspetjournals.org/content/60/1/114.full SO - Mol Pharmacol2001 Jul 01; 60 AB - Bovine adrenal zona fasciculata (AZF) cells express two types of K+-selective ion channels including a rapidly inactivating bKv1.4 current (IA) and an ATP-dependent noninactivating background current (IAC) 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 IAC 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 IA current. The reduction in IA current was observed only when patch pipettes contained ATP or other nucleotides at concentrations sufficient to support activation of IAC. Conversely, the nearly complete inhibition of IAC by corticotropin was accompanied by the coincident reappearance of functional IA channels. In the absence of IAC current, corticotropin failed to alter IA. 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 IA and IAC 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. IArapidly inactivating bKv1.4 current in bovine adrenal fasciculata cellsIACATP-activated, noninactivating potassium current in bovine adrenal fasciculata cellsAZFbovine adrenal zona fasciculataAMP-PNP5′-adenylyl-imidodiphosphateBAPTA1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acidDPBPdiphenylbutylpiperidineı̂the unitary currentNthe number of active channels in any given patchPochannel open probabilityToinitial time of recordingTMAXtime after IAC K+ current reaches a stable maximum amplitudeI-Vcurrent-voltage