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https://hdl.handle.net/2440/35549
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Type: | Journal article |
Title: | The role of the persistent Na+ current during cardiac ischemia and hypoxia |
Author: | Saint, D. |
Citation: | Journal of Cardiovascular Electrophysiology, 2006; 17(1):S96-S103 |
Publisher: | Futura Publ Co |
Issue Date: | 2006 |
ISSN: | 1045-3873 1540-8167 |
Statement of Responsibility: | David A. Saint |
Abstract: | Introduction: Inadequate or zero cardiac perfusion, if prolonged beyond about 10 minutes, can result in irreversible cell damage. Paradoxically, much of this damage occurs when perfusion is restored, and this appears to be linked to an uncontrolled rise in intracellular calcium. This article reviews the causes of this rise in calcium. Methods and results: Data that have arisen from a variety of techniques to measure intracellular ion concentrations in cardiac cells are reviewed. Fluorescence measurements in intact hearts and isolated cells show that the rise in [Ca2+]i is preceded by a rise in [Na+]i, a finding that has led to the coupled exchanger theory, which postulates that the high activity of the Na–H exchanger, as a result of intracellular acidification, increases [Na+]i and that this slows or reverses the Na–Ca exchanger. However, the [Na+]i appears to come from several sources: the Na–H exchanger, the Na–HCO3 symporter, and the persistent Na+ current, INa(p). The latter appears to be important because blockers of Na–H exchange (e.g., Cariporide) have been shown to be only partially protective against reperfusion damage, whereas TTX and other Na+ channel blockers offer equal or better protection. Patch clamp experiments in isolated cells have shown that INa(p) is increased by hypoxia, although the mechanisms are not known. Conclusion: Blockers of INa(p) may provide an alternative strategy for preventing reperfusion damage in myocardium, either alone or in combination with Na–H exchange blockers. |
Keywords: | cardiac hypoxia intracellular sodium ischemia sodium channel sodium current |
Description: | The definitive version is available at www.blackwell-synergy.com |
DOI: | 10.1111/j.1540-8167.2006.00390.x |
Published version: | http://www.blackwell-synergy.com/doi/abs/10.1111/j.1540-8167.2006.00390.x |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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