11502581

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3

Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and this inhibition is relieved by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. The role of PLB in regulating Ca(2+) release through ryanodine-sensitive Ca(2+) release channels, measured as Ca(2+) sparks, was examined using smooth muscle cells of cerebral arteries from PLB-deficient ("knockout") mice (PLB-KO). Ca(2+) sparks were monitored optically using the fluorescent Ca(2+) indicator fluo 3 or electrically by measuring transient large-conductance Ca(2+)-activated K(+) (BK) channel currents activated by Ca(2+) sparks. Basal Ca(2+) spark and transient BK current frequency were elevated in cerebral artery myocytes of PLB-KO mice. Forskolin, an activator of adenylyl cyclase, increased the frequency of Ca(2+) sparks and transient BK currents in cerebral arteries from control mice. However, forskolin had little effect on the frequency of Ca(2+) sparks and transient BK currents from PLB-KO cerebral arteries. Forskolin or PLB-KO increased SR Ca(2+) load, as measured by caffeine-induced Ca(2+) transients. This study provides the first evidence that PLB is critical for frequency modulation of Ca(2+) sparks and associated BK currents by PKA in smooth muscle.

eng

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MEDLINE

0363-6143

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C1029-37

pubmed-meshheading:11502581-Aniline Compounds, pubmed-meshheading:11502581-Animals, pubmed-meshheading:11502581-Caffeine, pubmed-meshheading:11502581-Calcium, pubmed-meshheading:11502581-Calcium Signaling, pubmed-meshheading:11502581-Calcium-Binding Proteins, pubmed-meshheading:11502581-Cerebral Arteries, pubmed-meshheading:11502581-Cyclic AMP, pubmed-meshheading:11502581-Enzyme Inhibitors, pubmed-meshheading:11502581-Forskolin, pubmed-meshheading:11502581-Large-Conductance Calcium-Activated Potassium Channels, pubmed-meshheading:11502581-Mice, pubmed-meshheading:11502581-Mice, Knockout, pubmed-meshheading:11502581-Models, Biological, pubmed-meshheading:11502581-Muscle, Smooth, Vascular, pubmed-meshheading:11502581-Potassium Channels, pubmed-meshheading:11502581-Potassium Channels, Calcium-Activated, pubmed-meshheading:11502581-Ryanodine, pubmed-meshheading:11502581-Thionucleotides, pubmed-meshheading:11502581-Xanthenes

Role of phospholamban in the modulation of arterial Ca(2+) sparks and Ca(2+)-activated K(+) channels by cAMP.

Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't