Role of phospholamban in the modulation of arterial Ca2+ sparks and Ca2+-activated K+ channels by cAMP

George C. Wellman, Luis Fernando Santana, Adrian D. Bonev, Mark T. Nelson

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca2+-ATPase, and this inhibition is relieved by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. The role of PLB in regulating Ca2+ release through ryanodine-sensitive Ca2+ release channels, measured as Ca2+ sparks, was examined using smooth muscle cells of cerebral arteries from PLB-deficient ("knockout") mice (PLB-KO). Ca2+ sparks were monitored optically using the fluorescent Ca2+ indicator fluo 3 or electrically by measuring transient large-conductance Ca2+-activated K+ (BK) channel currents activated by Ca2+ sparks. Basal Ca2+ 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 Ca2+ sparks and transient BK currents in cerebral arteries from control mice. However, forskolin had little effect on the frequency of Ca2+ sparks and transient BK currents from PLB-KO cerebral arteries. Forskolin or PLB-KO increased SR Ca2+ load, as measured by caffeine-induced Ca2+ transients. This study provides the first evidence that PLB is critical for frequency modulation of Ca2+ sparks and associated BK currents by PKA in smooth muscle.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number3 50-3
StatePublished - 2001
Externally publishedYes

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Calcium-Activated Potassium Channels
Electric sparks
Modulation
Cerebral Arteries
Colforsin
Sarcoplasmic Reticulum
Muscle
Large-Conductance Calcium-Activated Potassium Channels
Ryanodine
Phosphorylation
Calcium-Transporting ATPases
phospholamban
Frequency modulation
Cyclic AMP-Dependent Protein Kinases
Caffeine
Adenylyl Cyclases
Knockout Mice
Protein Kinases
Muscle Cells
Smooth Muscle Myocytes

Keywords

  • Adenosine 3′,5′-cyclic monophosphate
  • Calcium
  • cAMP-dependent protein kinase
  • Cerebral arteries
  • Ion channels
  • Potassium
  • Ryanodine receptors
  • Smooth muscle

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Role of phospholamban in the modulation of arterial Ca2+ sparks and Ca2+-activated K+ channels by cAMP. / Wellman, George C.; Santana, Luis Fernando; Bonev, Adrian D.; Nelson, Mark T.

In: American Journal of Physiology - Cell Physiology, Vol. 281, No. 3 50-3, 2001.

Research output: Contribution to journalArticle

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AB - Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca2+-ATPase, and this inhibition is relieved by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. The role of PLB in regulating Ca2+ release through ryanodine-sensitive Ca2+ release channels, measured as Ca2+ sparks, was examined using smooth muscle cells of cerebral arteries from PLB-deficient ("knockout") mice (PLB-KO). Ca2+ sparks were monitored optically using the fluorescent Ca2+ indicator fluo 3 or electrically by measuring transient large-conductance Ca2+-activated K+ (BK) channel currents activated by Ca2+ sparks. Basal Ca2+ 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 Ca2+ sparks and transient BK currents in cerebral arteries from control mice. However, forskolin had little effect on the frequency of Ca2+ sparks and transient BK currents from PLB-KO cerebral arteries. Forskolin or PLB-KO increased SR Ca2+ load, as measured by caffeine-induced Ca2+ transients. This study provides the first evidence that PLB is critical for frequency modulation of Ca2+ sparks and associated BK currents by PKA in smooth muscle.

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