Abstract
The effects of H-89, a potent and selective inhibitor of protein kinase A (PKA) on Ca(2+)-activated K(+) (BK(Ca)) channels in coronary arterial smooth muscle cells were examined using a patch-clamp technique. In inside-out configuration, H-89 increased the NP(o) of the BK(Ca) channel, but it reduced the dwell time of BK(Ca) currents. In whole-cell configuration, H-89 markedly increased BK(Ca) currents in a concentration-dependent manner. The EC(50) was 0.470+/-0.0741 microM based on dwell time, 0.582+/-0.0691 microM based on the NP(o), and 0.519+/-0.0295 microM based on the whole-cell current, respectively. H-85, which is an inactive form of H-89, increased BK(Ca) currents, similar to the result of H-89. The other PKA inhibitors (Rp-8-CPT-cAMPs and KT 5720) and protein phosphatase inhibitor (okadaic acid, 1 microM) had little effect on BK(Ca) currents and did not significantly alter the stimulatory effects of 1 microM H-89. These findings suggest that H-89 increases the BK(Ca) current independently of PKA.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carbazoles / pharmacology
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Coronary Circulation / drug effects
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Coronary Vessels / drug effects
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Coronary Vessels / metabolism
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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In Vitro Techniques
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Indoles / pharmacology
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Isoquinolines / pharmacology*
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Membrane Potentials / drug effects
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Muscle, Smooth, Vascular / drug effects*
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Muscle, Smooth, Vascular / metabolism
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Okadaic Acid / pharmacology
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Patch-Clamp Techniques
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Potassium Channels, Calcium-Activated / drug effects*
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Potassium Channels, Calcium-Activated / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Pyrroles / pharmacology
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Rabbits
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Sulfonamides / pharmacology*
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Thionucleotides / pharmacology
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Time Factors
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Vascular Resistance / drug effects
Substances
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Carbazoles
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Enzyme Inhibitors
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Indoles
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Isoquinolines
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Potassium Channels, Calcium-Activated
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Protein Kinase Inhibitors
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Pyrroles
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Sulfonamides
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Thionucleotides
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Okadaic Acid
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8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
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KT 5720
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Phosphoprotein Phosphatases
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide