Low extracellular K+ increases intracellular Ca2+ oscillation and injury by activating the reverse mode Na+-Ca2+ exchanger and inhibiting the Na+, K+ ATPase in rat cardiomyocytes.

The effects of low K(+) on post-ischemic reperfused heart cells are not clearly understood. Calcium overload is one of the major causes for myocardial reperfusion injury, the present study was to investigate the role of intracellular calcium oscillations in the effects of reperfusion with low K(+) on rat myocytes.
Ischemic myocytes were reperfused with Tyrode solution containing K(+) at 5.4 (control) or 3.0 mM (low K(+)) for 10 min. the changes of intracellular calcium was recorded by spectrofluorometry. The exclusion of trypan blue by myocytes served as indices of viability. Measurements of cell length, reverse-mode Na(+)-Ca(2+) exchanger (NCX) and Na(+), K(+) ATPase activity were performed.
Compared to control, myocytes reperfused with low K(+) had greater number of calcium oscillations and reverse-mode NCX activity, which were accompanied with decreased cell length recovery and cell viability. Reperfusion with KB-R7943, an inhibitor of reverse-mode NCX, attenuated the effects of low K(+) on all the parameters. Inhibition of Na(+), K(+) ATPase with Ouabain increased the susceptibility to calcium oscillations in myocytes reperfused with low K(+), which was accompanied with cell length shortening and decreased cell viability. Reperfusion with K(+) at 9.0 mM, which activated Na(+), K(+) ATPase, attenuated calcium oscillations, protected cell length recovery, and increased cell viability.
These results suggest that increased calcium oscillations mediate the exacerbating reperfusion injury with low K(+) on myocytes, and inhibition of Na(+), K(+) ATPase activity and increase of reverse-mode NCX activity contribute to these effects.
AuthorsFeng Wu, Geng-Ze Wei, Wei-Jie Li, Bing Liu, Jing-Jun Zhou, Hai-Chang Wang, Feng Gao
JournalInternational journal of cardiology (Int J Cardiol) Vol. 140 Issue 2 Pg. 161-8 (Apr 15 2010) ISSN: 1874-1754 [Electronic] Netherlands
PMID19059659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2008 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Enzyme Inhibitors
  • Sodium-Calcium Exchanger
  • sodium-calcium exchanger 1
  • Ouabain
  • Potassium Chloride
  • Sodium-Potassium-Exchanging ATPase
  • Calcium
  • Animals
  • Calcium (metabolism)
  • Calcium Signaling (drug effects, physiology)
  • Cell Survival (drug effects, physiology)
  • Cells, Cultured
  • Enzyme Inhibitors (pharmacology)
  • Heart Ventricles (cytology)
  • Male
  • Myocardial Reperfusion Injury (metabolism)
  • Myocytes, Cardiac (cytology, drug effects, metabolism)
  • Ouabain (pharmacology)
  • Potassium Chloride (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Calcium Exchanger (antagonists & inhibitors, metabolism)
  • Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors, metabolism)

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