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

This Article Full Text Full Text (PDF) All Versions of this Article: 286/1/L149    most recent 00207.2003v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Barman, S. A. Articles by White, R. E. Search for Related Content PubMed PubMed Citation Articles by Barman, S. A. Articles by White, R. E.

Protein kinase C inhibits BK_Ca channel activity in pulmonary arterial smooth muscle

Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912

Submitted 27 June 2003 ; accepted in final form 23 September 2003

Signaling mechanisms that elevate cyclic AMP (cAMP) activate large-conductance, calcium- and voltage-activated potassium (BK_Ca) channels in pulmonary vascular smooth muscle and cause pulmonary vasodilatation. BK_Ca channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (closing) of the BK_Ca channel has been implicated in the development of pulmonary vasoconstriction. Protein kinase C (PKC) causes pulmonary vasoconstriction, but little is known about the effect of PKC on BK_Ca channel activity. Accordingly, studies were done to determine the effect of PKC activation on cAMP-induced BK_Ca channel activity using patch-clamp studies in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), a recognized animal model of pulmonary hypertension. Forskolin (10 µM), a stimulator of adenylate cyclase and an activator of cAMP, opened BK_Ca channels in single FHR PASMC, which were blocked by the PKC activators phorbol 12-myristate 13-acetate (100 nM) and thymeleatoxin (100 nM). The inhibitory response by thymeleatoxin on forskolin-induced BK_Ca channel activity was blocked by Gö-6983, which selectively blocks the , , , , and PKC isozymes, and Gö-6976, which selectively inhibits PKC-, PKC-, and PKC-µ, but not by rottlerin, which selectively inhibits PKC-. Collectively, these results indicate that activation of specific PKC isozymes inhibits cAMP-induced activation of the BK_Ca channel in pulmonary arterial smooth muscle, which suggests a unique signaling pathway to modulate BK_Ca channels and subsequently cAMP-induced pulmonary vasodilatation.

high-conductance calcium- and voltage-activated potassium channel; protein kinase C isozymes; forskolin; cyclic adenosine 5'-monophosphate

This article has been cited by other articles:

				S. Zhu, D. D. Browning, R. E. White, D. Fulton, and S. A. Barman Mutation of protein kinase C phosphorylation site S1076 on {alpha}-subunits affects BKCa channel activity in HEK-293 cells Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L758 - L766. [Abstract] [Full Text] [PDF]

				W. Liu, Y. Wei, P. Sun, W.-H. Wang, T. R. Kleyman, and L. M. Satlin Mechanoregulation of BK channel activity in the mammalian cortical collecting duct: role of protein kinases A and C Am J Physiol Renal Physiol, October 1, 2009; 297(4): F904 - F915. [Abstract] [Full Text] [PDF]

				S. Dai, D. D. Hall, and J. W. Hell Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels Physiol Rev, April 1, 2009; 89(2): 411 - 452. [Abstract] [Full Text] [PDF]

				T. Vaithianathan, A. Bukiya, J. Liu, P. Liu, M. Asuncion-Chin, Z. Fan, and A. Dopico Direct Regulation of BK Channels by Phosphatidylinositol 4,5-Bisphosphate as a Novel Signaling Pathway J. Gen. Physiol., July 1, 2008; 132(1): 13 - 28. [Abstract] [Full Text] [PDF]

				Shu Zhu, R. E. White, and S. A. Barman Original Research: Role of phosphodiesterases in modulation of BKCa channels in hypertensive pulmonary arterial smooth muscle Therapeutic Advances in Respiratory Disease, June 1, 2008; 2(3): 119 - 127. [Abstract] [PDF]

				H. Syyong, C. Cheung, D. Solomon, C. Y. Seow, and K. H. Kuo Adaptive response of pulmonary arterial smooth muscle to length change J Appl Physiol, April 1, 2008; 104(4): 1014 - 1020. [Abstract] [Full Text] [PDF]

				S. A. Barman Vasoconstrictor effect of endothelin-1 on hypertensive pulmonary arterial smooth muscle involves Rho-kinase and protein kinase C Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L472 - L479. [Abstract] [Full Text] [PDF]

				C. K. Isacson, Q. Lu, R. H. Karas, and D. H. Cox RACK1 is a BKCa channel binding protein Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1459 - C1466. [Abstract] [Full Text] [PDF]

				E. Resnik, J. Herron, M. Keck, D. Sukovich, B. Linden, and D. N. Cornfield Chronic intrauterine pulmonary hypertension selectively modifies pulmonary artery smooth muscle cell gene expression Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L426 - L433. [Abstract] [Full Text] [PDF]

				T. L. Pallone, C. Cao, and Z. Zhang Inhibition of K+ conductance in descending vasa recta pericytes by ANG II Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1213 - F1222. [Abstract] [Full Text] [PDF]