Effect of PKC isozyme inhibition on forskolin-induced activation of BKCa channels in rat pulmonary arterial smooth muscle.

Lung
Shu ZhuScott A Barman

Abstract

Signaling mechanisms that elevate cyclic AMP (cAMP) activate large-conductance, calcium- and voltage-activated potassium (BKCa) channels in vascular smooth muscle and cause vasodilatation. In pulmonary vascular smooth muscle (PVSM), BKCa channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (closing) of the BKCa channel causes pulmonary vasoconstriction. Protein kinase C (PKC) modulates BKCa channels in systemic vascular smooth muscle, but little is known about the effect of PKC on BKCa channel activity in PVSM. A novel finding from our laboratory showed that PKC activates BKCa channels in rat pulmonary arterial smooth muscle and, having observed that cAMP-elevating agents also open BKCa channels, we hypothesized that PKC may open BKCa channels via a cAMP-dependent mechanism. Forskolin (10 microM), an activator of adenylyl cyclase, which increases cAMP concentration, opened BKCa channels in single pulmonary arterial smooth muscle cells (PASMC) of the Sprague-Dawley rat. The effect of forskolin was completely blocked by the PKC inhibitor Go 6983, which selectively blocks the alpha, beta, delta, gamma, and zeta PKC isozymes, and, by rottlerin, which selectively inhibits PKCdelta, and par...Continue Reading

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Citations

Jul 14, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shu ZhuScott A Barman
Feb 11, 2011·Journal of Neurophysiology·Ingrid van Welie, Sascha du Lac
Feb 2, 2012·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Yiwei ShiJunfa Li
Feb 5, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Biny K JosephSung W Rhee
Sep 24, 2010·Kidney International·Roland S Wu, Steven O Marx
Nov 10, 2007·Biochemical and Biophysical Research Communications·Ji-Yoen Kim, Chul-Seung Park
Jul 14, 2010·Biochimica Et Biophysica Acta·Hanna M PeltonenGeneviève Bart
Jun 20, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ahmed F El-YazbiEdwin E Daniel
Dec 20, 2013·American Journal of Physiology. Cell Physiology·Kiril L HristovGeorgi V Petkov
Sep 1, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chuen-Mao YangLi-Der Hsiao

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