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

Shu Zhu, Richard E. White, Scott A Barman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Signaling mechanisms that elevate cyclic AMP (cAMP) activate large-conductance, calcium- and voltage-activated potassium (BK Ca ) channels in vascular smooth muscle and cause vasodilatation. In pulmonary vascular smooth muscle (PVSM), BK Ca channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (closing) of the BK Ca channel causes pulmonary vasoconstriction. Protein kinase C (PKC) modulates BK Ca channels in systemic vascular smooth muscle, but little is known about the effect of PKC on BK Ca channel activity in PVSM. A novel finding from our laboratory showed that PKC activates BK Ca channels in rat pulmonary arterial smooth muscle and, having observed that cAMP-elevating agents also open BK Ca channels, we hypothesized that PKC may open BK Ca channels via a cAMP-dependent mechanism. Forskolin (10 μM), an activator of adenylyl cyclase, which increases cAMP concentration, opened BK Ca 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 BK Ca channels in PASMC, which suggests that a signaling pathway involving PKC activation and cAMP exists in pulmonary arterial smooth muscle to open BK Ca channels.

Original languageEnglish (US)
Pages (from-to)89-97
Number of pages9
JournalLung
Volume184
Issue number2
DOIs
StatePublished - Apr 1 2006

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Colforsin
Protein Kinase C
Isoenzymes
Smooth Muscle
Lung
Cyclic AMP
Vascular Smooth Muscle
Smooth Muscle Myocytes
Protein C Inhibitor
Protein Kinase Inhibitors
Vasoconstriction
Adenylyl Cyclases
Vasodilation
Sprague Dawley Rats
Potassium
Arterial Pressure

Keywords

  • BK channels
  • Forskolin
  • Protein kinase C
  • Pulmonary
  • cAMP

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effect of PKC isozyme inhibition on forskolin-induced activation of BK Ca channels in rat pulmonary arterial smooth muscle . / Zhu, Shu; White, Richard E.; Barman, Scott A.

In: Lung, Vol. 184, No. 2, 01.04.2006, p. 89-97.

Research output: Contribution to journalArticle

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