Altered calcium sensitivity contributes to enhanced contractility of collateral-dependent coronary arteries

Cristine L. Heaps, Janet L. Parker, Michael Sturek, Douglas K. Bowles

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Coronary arteries distal to chronic occlusion exhibit enhanced vasoconstriction and impaired relaxation compared with nonoccluded arteries. In this study, we tested the hypotheses that an increase in peak Ca2+ channel current density and/or increased Ca2+ sensitivity contributes to altered contractility in collateral-dependent coronary arteries. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery (LCX) of female miniature swine. Segments of epicardial arteries (∼1 mm luminal diameter) were isolated from the LCX and nonoccluded left anterior descending (LAD) arteries 24 wk after Ameroid placement. Contractile responses to depolarization (10-100 mM KCl) were significantly enhanced in LCX compared with size-matched LAD arterial rings [concentration of KCl causing 50% of the maximal contractile response (EC50); LAD = 41.7 ± 2.3, LCX = 34.3 ± 2.7 mM]. However, peak Ca2+ channel current was not altered in isolated smooth muscle cells from LCX compared with LAD (-5.29 ± 0.42 vs. -5.68 ± 0.55 pA/pF, respectively). Furthermore, whereas half-maximal activation of Ca2+ channel current occurred at nearly the same membrane potential in LAD and LCX, half-maximal inactivation was shifted to a more positive membrane potential in LCX cells. Simultaneous measures of contractile tension and intracellular free Ca2+ (fura 2) levels in arterial rings revealed that significantly more tension was produced per unit change in fura 2 ratio in LCX compared with LAD in response to KCl but not during receptor-agonist stimulation with endothelin-1. Taken together, our data indicate that coronary arteries distal to chronic occlusion display increased Ca2+ sensitivity in response to high KCl-induced depolarization, independent of changes in whole cell peak Ca2+ channel current. Unaltered Ca2+ sensitivity in endothelin-stimulated arteries suggests more than one mechanism regulating Ca2+ sensitization in coronary smooth muscle.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalJournal of Applied Physiology
Volume97
Issue number1
DOIs
StatePublished - Jul 2004

Keywords

  • Ca channel
  • Ca current
  • Fura 2
  • Smooth muscle
  • Voltage clamp

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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