Ca2+ channels, ryanodine receptors and Ca2+-activated K+ channels: A functional unit for regulating arterial tone

J. H. Jaggar, G. C. Wellman, T. J. Heppner, V. A. Porter, G. J. Perez, M. Gollasch, T. Kleppisch, M. Rubart, A. S. Stevenson, W. J. Lederer, H. J. Knot, A. D. Bonev, Mark T. Nelson

Research output: Contribution to journalArticle

241 Scopus citations

Abstract

Local calcium transients ('Ca2+ sparks') are thought to be elementary Ca2+ signals in heart, skeletal and smooth muscle cells. Ca2+ sparks result from the opening of a single, or the coordinated opening of many, tightly clustered ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In arterial smooth muscle, Ca2+ sparks appear to be involved in opposing the tonic contraction of the blood vessel. Intravascular pressure causes a graded membrane potential depolarization to approximately -40 mV, an elevation of arterial wall [Ca2+](i) and contraction ('myogenic tone') of arteries. Ca2+ sparks activate calcium-sensitive K+ (K(Ca)) channels in the sarcolemmal membrane to cause membrane hyperpolarization, which opposes the pressure induced depolarization. Thus, inhibition of Ca2+ sparks by ryanodine, or of K(Ca) channels by iberiotoxin, leads to membrane depolarization, activation of L-type voltage-gated Ca2+ channels, and vasoconstriction. Conversely, activation of Ca2+ sparks can lead to vasodilation through activation of K(Ca) channels. Our recent work is aimed at studying the properties and roles of Ca2+ sparks in the regulation of arterial smooth muscle function. The modulation of Ca2+ spark frequency and amplitude by membrane potential, cyclic nucleotides and protein kinase C will be explored. The role of local Ca2+ entry through voltage-dependent Ca2+ channels in the regulation of Ca2+ spark properties will also be examined. Finally, using functional evidence from cardiac myocytes, and histological evidence from smooth muscle, we shall explore whether Ca2+ channels, RyR channels, and K(Ca) channels function as a coupled unit, through Ca2+ acid voltage, to regulate arterial smooth muscle membrane potential and vascular tone.

Original languageEnglish (US)
Pages (from-to)577-587
Number of pages11
JournalActa Physiologica Scandinavica
Volume164
Issue number4
DOIs
StatePublished - 1998

Keywords

  • Ca sparks
  • Ca-ATPase
  • Membrane potential
  • Protein kinase A
  • Protein kinase C
  • Protein kinase G
  • Sarcoplasmic reticulum
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology

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