Title

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

Document Type

Article

Publication Date

2006

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 µM), 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 α, β, δ, γ, and ζ PKC isozymes, and, by rottlerin, which selectively inhibits PKCδ, and partially blocked by Go 6976, which selectively inhibits PKCα PKCβ, and PKCμ. These results indicate that specific PKC isozymes mediate forskolin-induced activation of BKCa channels in PASMC, which suggests that a signaling pathway involving PKC activation and cAMP exists in pulmonary arterial smooth muscle to open BKCa channels. © Springer Science+Business Media, Inc. 2006.

Publication Title

Lung

Volume

184

Issue

2

First Page

89

Last Page

97

Comments

This article was published in Lung, Volume 184, Issue 2, Pages 89-97.

The published version is available at http://dx.doi.org/10.1007/s00408-005-2567-y.

Copyright © 2006 Springer.

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