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Role of phospholamban in the modulation of arterial Ca(2+) sparks and Ca(2+)-activated K(+) channels by cAMP.
Wellman G, Santana L, Bonev A, Nelson MT
American Journal of Physiology-Cell Physiology. 2001;281( 3):C1029-37.
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Abstract
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.
Keyword(s)
Aniline Compounds; Animals; Large-Conductance Calcium-Activated Potassium Channels; Mice; Mice, Knockout; Models, Biological; Potassium Channels, Calcium-Activated; Xanthenes; analogs & derivatives: Cyclic AMP; deficiency: Calcium-Binding Proteins; drug effects: Calcium Signaling; drug effects: Cerebral Arteries; drug effects: Muscle, Smooth, Vascular; pharmacology: Caffeine; pharmacology: Enzyme Inhibitors; pharmacology: Forskolin; pharmacology: Ryanodine; pharmacology: Thionucleotides; physiology: Calcium; physiology: Potassium Channels