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Updated: Aug 26, 2026
Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Altered calcium sensitivity contributes to enhanced contractility of collateral-dependent coronary arteries
Cristine L Heaps1, Janet L Parker, Michael Sturek
1Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA. heapsc@missouri.edu
Insights
Coronary arteries near chronic blockages show stronger constriction due to increased calcium sensitivity, not higher calcium channel activity. This impacts blood flow regulation in these vital vessels.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Smooth Muscle Pharmacology
Background:
- Coronary arteries distal to chronic occlusions exhibit altered contractility, with enhanced vasoconstriction and impaired relaxation.
- The underlying mechanisms, particularly the role of calcium (Ca2+) handling, remain incompletely understood.
Purpose of the Study:
- To test the hypotheses that increased peak Ca2+ channel current density and/or Ca2+ sensitivity contribute to altered contractility in collateral-dependent coronary arteries.
- To investigate the specific contributions of Ca2+ channel function and Ca2+ sensitivity to contractile responses in arteries affected by chronic occlusion.
Main Methods:
- Surgical placement of Ameroid occluders in female miniature swine to induce chronic coronary artery occlusion.
- Isolation and functional assessment of epicardial coronary arterial rings (left circumflex artery - LCX, and left anterior descending artery - LAD).
- Measurement of contractile responses to KCl, Ca2+ channel currents in isolated smooth muscle cells, and simultaneous tension and intracellular Ca2+ (fura 2) measurements.
Main Results:
- Contractile responses to depolarization (KCl) were significantly enhanced in collateral-dependent LCX arteries compared to non-occluded LAD arteries.
- Peak Ca2+ channel current density was not altered in smooth muscle cells from LCX compared to LAD arteries.
- Arterial rings from LCX arteries produced significantly more tension per unit change in intracellular Ca2+ during KCl stimulation, indicating increased Ca2+ sensitivity.
Conclusions:
- Coronary arteries distal to chronic occlusion display increased Ca2+ sensitivity in response to high KCl-induced depolarization.
- This increased Ca2+ sensitivity is independent of changes in whole-cell peak Ca2+ channel current density.
- The findings suggest that altered Ca2+ sensitivity, rather than altered Ca2+ channel current, is a key mechanism for enhanced contractility in collateral-dependent coronary arteries, with potential for multiple regulatory mechanisms involved.
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 Ca(2+) channel current density and/or increased Ca(2+) 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 ( approximately 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 (EC(50)); LAD = 41.7 +/- 2.3, LCX = 34.3 +/- 2.7 mM]. However, peak Ca(2+) 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 Ca(2+) 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 Ca(2+) (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 Ca(2+) sensitivity in response to high KCl-induced depolarization, independent of changes in whole cell peak Ca(2+) channel current. Unaltered Ca(2+) sensitivity in endothelin-stimulated arteries suggests more than one mechanism regulating Ca(2+) sensitization in coronary smooth muscle.
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