Kinase activation and smooth muscle contraction in the presence and absence of calcium

Glenn Whitney, Doug Throckmorton, Carlos Isales, Yo Takuwa, Jennifer Yeh, Howard Rasmussen, Colleen Brophy

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Purpose: The intracellular signalling mechanisms that modulate the sustained vascular smooth muscle contractions that occur with vasospasm are not well understood. The purpose of this investigation was to examine cell signalling mechanisms that account for sustained vascular smooth muscle contraction, independent of increases in intracellular Ca2+ concentrations ([Ca2+ ]i). Methods: Fresh bovine carotid artery smooth muscles contractile responses were examined in a muscle bath. [Ca2+ ]i was depleted by use of the extracellular Ca2+ chelator, ethylene glycol-bis(ß-aminoethylether) N, N, N′, N′-tetraacetic acid and the intracellular chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′,-tetraacetic acid. Results: In Ca2+ -free conditions, depolarizing the membrane with high extracellular KCI failed to elicit a contraction. In addition, in Ca2+-free conditions the ([Ca2+]i) was less than 10 nmol/L as determined with the Ca2+-indicator, Fura 2. The protein kinase C (PKC) activator, phorbol 12, 13-dibutyrate (PDBu), induced slowly developing sustained contractions in bovine carotid artery smooth muscle, and the magnitude of the contractile response to PDBu (10 nmol/L to 10 μmol/L) was the same in the presence and absence of Ca2+ . PDBu induced contractions in Ca2+ -free conditions were not inhibited by the myosin light chain kinase inhibitor, ML-9 (50 μmol/L), but were inhibited by the PKC inhibitor, staurosporine (50 nmol/L). Conclusions: These data suggest that vascular smooth muscle contractions can occur under conditions where the [Ca2+ ]i is low and fixed and that these contractions may be mediated by PKC. (J VASC SURG 1995;22:37-44.).

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalJournal of Vascular Surgery
Volume22
Issue number1
DOIs
StatePublished - Jul 1995
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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