Burn injury decreases myocardial Na-K-ATPase activity: role of PKC inhibition.

Abstract

Cardiomyocyte sodium accumulation after burn injury precedes the development of myocardial contractile dysfunction. The present study examined the effects of burn injury on Na-K-ATPase activity in adult rat hearts after major burn injury and explored the hypothesis that burn-related changes in myocardial Na-K-ATPase activity are PKC dependent. A third-degree burn injury (or sham burn) was given over 40% total body surface area, and rats received lactated Ringer solution (4 ml.kg(-1).% burn(-1)). Subgroups of rats were killed 2, 4, or 24 h after burn (n = 6 rats/time period), hearts were homogenized, and Na-K-ATPase activity was determined from ouabain-sensitive phosphate generation from ATP by cardiac sarcolemmal vesicles. Additional groups of rats were studied at several times after burn to determine the time course of myocyte sodium loading and the time course of myocardial dysfunction. Additional groups of sham burn-injured and burn-injured rats were given calphostin, an inhibitor of PKC, and Na-K-ATPase activity, cell Na(+), and myocardial function were measured. Burn injury caused a progressive rise in cardiomyocyte Na(+), and myocardial Na-K-ATPase activity progressively decreased after burn, while PKC activity progressively rose. Administration of calphostin to inhibit PKC activity prevented both the burn-related decrease in myocardial Na-K-ATPase and the rise in intracellular Na(+) and improved postburn myocardial contractile performance. We conclude that burn-related inhibition of Na-K-ATPase likely contributes to the cardiomyocyte accumulation of intracellular Na(+). Since intracellular Na(+) is one determinant of electrical-mechanical recovery after insults such as burn injury, burn-related inhibition of Na-K-ATPase may be critical in postburn recovery of myocardial contractile function.

• Authors: Jureta W Horton, Jing Tan, D Jean White, David L Maass
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 293 Issue 4 Pg. R1684-92 (Oct 2007) ISSN: 0363-6119 [Print] United States
• PMID: 17634196 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Enzyme Inhibitors
• Naphthalenes
• calphostin complex
• Sodium
• Protein Kinase C
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Burns (enzymology)
• Cytokines (metabolism)
• Enzyme Inhibitors (pharmacology)
• Male
• Myocardial Contraction (physiology)
• Myocardium (enzymology)
• Myocytes, Cardiac (drug effects, metabolism)
• Naphthalenes (pharmacology)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Rats
• Rats, Sprague-Dawley
• Sodium (metabolism)
• Sodium-Potassium-Exchanging ATPase (metabolism)