A potassium channel underlying cortisol secretion in adrenocortical cells
Sanjay Danthi (Mathematical Biosciences Institute, The Ohio State University)
(December 4, 2002 12:30 AM - 1:30 AM)
Adrenal Zona Fasciculata (AZF) cells in the adrenal cortex secrete cortisol in response to ACTH, a hormone released by the pituitary gland. ACTH acts by depolarizing these cells leading to Ca+2 influx through T-type Ca+2 channels, which subsequently causes Ca+2 dependent cortisol release. Our laboratory has discovered an ATP activated, non-inactivating background K+ channel (Iac/TREK-1/KCNK2) in bovine AZF cells that serves to set the resting membrane potential of the cell (Mlinar et al, 1993; Enyeart et al, 1997). ACTH inhibits this channel at physiological concentrations leading to membrane depolarization (Mlinar et al, 1993). Thus our laboratory has identified the link between ACTH and cortisol secretion. In my talk I will discuss some of the important properties of this channel such as nucleotide dependence, agonists and antagonists and its cloning (Xu and Enyeart, 2001; Enyeart et al, 2002.). I will also briefly talk about some of the electrophysiological techniques that I have used in my work such as whole cell and single channel patch clamp recordings. Finally I would mention our idea of modeling the ionic currents in the bovine AZF cells to generate a model that would identify possible membrane potential oscillations and help determine the voltage dependent entry of Ca+2 into the cell necessary for optimal release of cortisol.
Mlinar B, Biagi BA, Enyeart JJ. A novel K+ current inhibited by adrenocorticotropic hormone and angiotensin II in adrenal cortical cells. J Biol Chem. 1993 Apr 25; 268(12): 8640-4.
Enyeart JJ, Gomora JC, Xu L, Enyeart JA. Adenosine triphosphate activates a non-inactivating K+ current in adrenal cortical cells through nonhydrolytic binding. J Gen Physiol. 1997 Dec; 110(6): 679-92.
Xu, L and Enyeart JA. Properties of ATP-dependent K+ channels in adrenocortical cells. Am J Physiol Cell Physiol. 2001 Jan; 280(1): C199-215.
Enyeart JJ, Xu L, Danthi S, Enyeart JA. An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1. J Biol Chem. 2002 Oct 3.