HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 51, 49186-49199, December 20, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/51/49186    most recent M207233200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Enyeart, J. J. Articles by Enyeart, J. A. Search for Related Content PubMed PubMed Citation Articles by Enyeart, J. J. Articles by Enyeart, J. A. Social Bookmarking                      What's this?

An ACTH- and ATP-regulated Background K⁺ Channel in Adrenocortical Cells Is TREK-1^*

John J. Enyeart, Lin Xu, Sanjay Danthi^§, and Judith A. Enyeart

From the Department of Neuroscience, The Ohio State University, College of Medicine, Columbus, Ohio 43210-1239

Bovine adrenal zona fasciculata (AZF) cells express a background K⁺ channel (I_AC) that sets the resting potential and acts pivotally in ACTH-stimulated cortisol secretion. We have cloned a bTREK-1 (KCNK2) tandem-pore K⁺ channel cDNA from AZF cells with properties that identify it as the native I_AC. The bTREK-1 cDNA is expressed robustly in AZF cells and includes transcripts of 4.9, 3.6, and 2.8 kb. In patch clamp recordings made from transiently transfected cells, bTREK-1 displayed distinctive properties of I_AC in AZF cells. Specifically, bTREK-1 currents were outwardly rectifying with a large instantaneous and smaller time-dependent component. Similar to I_AC, bTREK-1 increased spontaneously in amplitude over many minutes of whole cell recording and was blocked potently by Ca²⁺ antagonists including penfluridol and mibefradil and by 8-(4-chlorophenylthio)-cAMP. Unitary TREK-1 and I_AC currents were nearly identical in amplitude. The native I_AC current, in turn, displayed properties that together are specific to TREK-1 K⁺ channels. These include activation by intracellular acidification, enhancement by the neuroprotective agent riluzole, and outward rectification. bTREK-1 current differed from native K⁺ current only in its lack of ATP dependence. In contrast to I_AC, the current density of bTREK-1 in human embryonic kidney-293 cells was not increased by raising pipette ATP from 0.1 to 5 mM. Further, the enhancement of I_AC current in AZF cells by low pH and riluzole was facilitated by, and dependent on, ATP at millimolar concentrations in the pipette solution. Overall, these results establish the identity of I_AC K⁺ channels, demonstrate the expression of bTREK-1 in a specific endocrine cell, identify potent new TREK-1 antagonists, and assign a pivotal role for these tandem-pore channels in the physiology of cortisol secretion. The activation of I_AC by ATP indicates that native bTREK-1 channels may function as sensors that couple the metabolic state of the cell to membrane potential, perhaps through an associated ATP-binding protein.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY148474.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				E. Nanou, A. Kyriakatos, P. Kettunen, and A. El Manira Separate signalling mechanisms underlie mGluR1 modulation of leak channels and NMDA receptors in the network underlying locomotion J. Physiol., June 15, 2009; 587(12): 3001 - 3008. [Abstract] [Full Text] [PDF]

				H. Liu, J. A. Enyeart, and J. J. Enyeart ACTH Inhibits bTREK-1 K+ Channels through Multiple cAMP-dependent Signaling Pathways J. Gen. Physiol., August 1, 2008; 132(2): 279 - 294. [Abstract] [Full Text] [PDF]

				H. Liu, J. A. Enyeart, and J. J. Enyeart Potent Inhibition of Native TREK-1 K+ Channels by Selected Dihydropyridine Ca2+ Channel Antagonists J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 39 - 48. [Abstract] [Full Text] [PDF]

				R. Varas, C. N. Wyatt, and K. J. Buckler Modulation of TASK-like background potassium channels in rat arterial chemoreceptor cells by intracellular ATP and other nucleotides J. Physiol., September 1, 2007; 583(2): 521 - 536. [Abstract] [Full Text] [PDF]

				H. Liu, J. A. Enyeart, and J. J. Enyeart Angiotensin II inhibits native bTREK-1 K+ channels through a PLC-, kinase C-, and PIP2-independent pathway requiring ATP hydrolysis Am J Physiol Cell Physiol, August 1, 2007; 293(2): C682 - C695. [Abstract] [Full Text] [PDF]

				G. Czirjak and P. Enyedi Zinc and Mercuric Ions Distinguish TRESK from the Other Two-Pore-Domain K+ Channels Mol. Pharmacol., March 1, 2006; 69(3): 1024 - 1032. [Abstract] [Full Text] [PDF]

				J. J. Enyeart, S. J. Danthi, H. Liu, and J. A. Enyeart Angiotensin II Inhibits bTREK-1 K+ Channels in Adrenocortical Cells by Separate Ca2+- and ATP Hydrolysis-dependent Mechanisms J. Biol. Chem., September 2, 2005; 280(35): 30814 - 30828. [Abstract] [Full Text] [PDF]

				D. Kang, C. Choe, and D. Kim Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK J. Physiol., April 1, 2005; 564(1): 103 - 116. [Abstract] [Full Text] [PDF]

				J. Chemin, A. Patel, F. Duprat, M. Zanzouri, M. Lazdunski, and E. Honore Lysophosphatidic Acid-operated K+ Channels J. Biol. Chem., February 11, 2005; 280(6): 4415 - 4421. [Abstract] [Full Text] [PDF]

				J. A. Enyeart, S. J. Danthi, and J. J. Enyeart TREK-1 K+ channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1154 - E1165. [Abstract] [Full Text] [PDF]

				S. Danthi, J. A. Enyeart, and J. J. Enyeart Caffeic Acid Esters Activate TREK-1 Potassium Channels and Inhibit Depolarization-Dependent Secretion Mol. Pharmacol., March 1, 2004; 65(3): 599 - 610. [Abstract] [Full Text] [PDF]

				B. A. Williams and K. J. Buckler Biophysical properties and metabolic regulation of a TASK-like potassium channel in rat carotid body type 1 cells Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L221 - L230. [Abstract] [Full Text] [PDF]

				J. A. Enyeart, S. Danthi, and J. J. Enyeart Corticotropin Induces the Expression of TREK-1 mRNA and K+ Current in Adrenocortical Cells Mol. Pharmacol., July 1, 2003; 64(1): 132 - 142. [Abstract] [Full Text] [PDF]