This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lotshaw, D. P. Search for Related Content PubMed PubMed Citation Articles by Lotshaw, D. P.

Effects of K⁺ Channel Blockers on K⁺ Channels, Membrane Potential, and Aldosterone Secretion in Rat Adrenal Zona Glomerulosa Cells¹

Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60115

Address all correspondence and requests for reprints to: Dr. David P. Lotshaw, Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60112.

The hypothesis that angiotensin II (ANG II)-induced aldosterone secretion is mediated through inhibition of plasma membrane K⁺ channels was examined by measuring the effects of K⁺ channel blockers on K⁺ currents, membrane potential, and aldosterone secretion in rat adrenal glomerulosa cells. Effective K⁺ channel blockers were identified and studied using patch clamp methods on isolated glomerulosa cells in cell culture. Extracellular Cs⁺ (2–20 mM) caused a voltage-dependent inhibition of macroscopic K⁺ currents, exhibiting an apparent K_d of 2 mM for blockade of K⁺ current at membrane potentials near the K⁺ equilibrium potential. Outward K⁺ current opposed the Cs⁺ block, imparting a steep voltage dependence to this block. In single channel studies Cs⁺ blocked inward, but not outward, unitary currents through ANG II-regulated weakly voltage-dependent K⁺ channels, which are thought to control resting membrane potential. Cs⁺ reversibly depolarized the resting membrane potential at concentrations greater than or equal to the apparent K_d for K⁺ conductance inhibition (2 mM). Depolarization consisted of a slow, maintained phase proportional to Cs⁺ concentration superimposed with 2- to 5-mV transient depolarizing events. Cs⁺ induced a Ca²⁺-dependent stimulation of aldosterone secretion in acutely dissociated cells, exhibiting an EC₅₀ of approximately 3 mM. Maximal Cs⁺-induced secretion was quantitatively similar to 1 nM ANG II- or 8 mM K⁺-induced secretion. Cs⁺-induced secretion was not additive with that of ANG II. K⁺ channel blockers that did not inhibit weakly voltage-dependent K⁺ channels at rest (quinidine, apamin, and charybdotoxin) did not cause depolarization or stimulate aldosterone secretion. Furthermore, charybdotoxin did not significantly affect ANG II-induced aldosterone secretion, indicating that Ca²⁺-dependent maxi-K⁺ channels did not contribute to the control of aldosterone secretion in acutely dissociated cells. These data strongly support involvement of weakly voltage-dependent K⁺ channels in ANG II-induced aldosterone secretion, but also implicate roles for other channel classes in controlling membrane potential during ANG II-induced aldosterone secretion.

This article has been cited by other articles:

				L. A. Davies, C. Hu, N. A. Guagliardo, N. Sen, X. Chen, E. M. Talley, R. M. Carey, D. A. Bayliss, and P. Q. Barrett TASK channel deletion in mice causes primary hyperaldosteronism PNAS, February 12, 2008; 105(6): 2203 - 2208. [Abstract] [Full Text] [PDF]

				M. Sausbier, C. Arntz, I. Bucurenciu, H. Zhao, X.-B. Zhou, U. Sausbier, S. Feil, S. Kamm, K. Essin, C. A. Sailer, et al. Elevated Blood Pressure Linked to Primary Hyperaldosteronism and Impaired Vasodilation in BK Channel-Deficient Mice Circulation, July 5, 2005; 112(1): 60 - 68. [Abstract] [Full Text] [PDF]

				A. SPAT and L. HUNYADY Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways Physiol Rev, April 1, 2004; 84(2): 489 - 539. [Abstract] [Full Text] [PDF]

				G. Czirjak and P. Enyedi TASK-3 Dominates the Background Potassium Conductance in Rat Adrenal Glomerulosa Cells Mol. Endocrinol., March 1, 2002; 16(3): 621 - 629. [Abstract] [Full Text] [PDF]

				I. Arrighi, M. Bloch-Faure, F. Grahammer, M. Bleich, R. Warth, R. Mengual, M.-D. Drici, J. Barhanin, and P. Meneton Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome PNAS, June 28, 2001; (2001) 141233398. [Abstract] [Full Text] [PDF]

				T. Kigoshi, N. Imaizumi, J. Yoshida, A. Nakagawa, S. Nakano, M. Nishio, and K. Uchida Involvement of tyrosine kinase in citrate-stimulated aldosterone production in bovine glomerulosa cells Am J Physiol Endocrinol Metab, July 1, 2000; 279(1): E140 - E145. [Abstract] [Full Text] [PDF]

				M. Thoby-Brisson, P. Telgkamp, and J.-M. Ramirez The Role of the Hyperpolarization-Activated Current in Modulating Rhythmic Activity in the Isolated Respiratory Network of Mice J. Neurosci., April 15, 2000; 20(8): 2994 - 3005. [Abstract] [Full Text] [PDF]

				X.-L. Chen, D. A. Bayliss, R. J. Fern, and P. Q. Barrett A role for T-type Ca2+ channels in the synergistic control of aldosterone production by ANG II and K+ Am J Physiol Renal Physiol, May 1, 1999; 276(5): F674 - F683. [Abstract] [Full Text] [PDF]

				I. Arrighi, M. Bloch-Faure, F. Grahammer, M. Bleich, R. Warth, R. Mengual, M.-D. Drici, J. Barhanin, and P. Meneton Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome PNAS, July 17, 2001; 98(15): 8792 - 8797. [Abstract] [Full Text] [PDF]