Inhibition of protein kinase C (PKC) increases Na,K-ATPase activity and limits sodium accumulation in the ischemic rat heart

Saul Schaefer, R. Ramasamy, J. A. Lundmark

Research output: Contribution to journalArticle

Abstract

Myocardial ischemia increases intracellular sodium ([Na]i). Since PKC has been shown to phosphorylate and lower Na,K-ATPase activity, we postulated that PKC inhibition would increase Na,K-ATPase activity and reduce [Na]i during ischemia. To test this hypothesis, isolated rat hearts had 30 min of global ischemia with and without pre-treatment with the specific PKC inhibitor chelerythrine 1 μM (CHEL). Intracellular pH, PCr, ATP, and [Na]i (31P and 23Na NMR spectroscopy) as well as Na,K-ATPase and PKC activity (biochemical assay) were measured. CHEL hearts had lower infarct size when compared with control (creatine kinase release: 48 ± 5 vs. 705 ± 72 IU/gdw; p = .008), but not different acidosis (nadir pH: 6.16 ± .05 CHEL vs 6.09 ± .03 control) or ATP depletion. The rise in [Na]i during ischemia was reduced in CHEL hearts (peak [Na]i CHEL: 21.5 ± 1.2 mM, control: 32.5 ± 0.8 mM; p < .0001), while Na,K-ATPase activity was significantly increased (5.5 ± 0.5 vs 4.1 ± 0.4 mg ADP/hr/mg protein; p = .0001). CHEL significantly reduced PKC activity (membrane and cytosolic fractions) under baseline conditions. These data support the hypothesis that PKC inhibition can reduce [Na]i overload via an increase in Na,K-ATPase activity, thus limiting ischemic injury.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997

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sodium-potassium-exchanging ATPase
protein kinase C
Protein Kinase C
Adenosine Triphosphatases
Rats
Sodium
heart
sodium
rats
ischemia
Ischemia
Adenosine Triphosphate
Protein C Inhibitor
infarction
creatine kinase
acidosis
Protein Kinase Inhibitors
Creatine Kinase
myocardial ischemia
Acidosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Inhibition of protein kinase C (PKC) increases Na,K-ATPase activity and limits sodium accumulation in the ischemic rat heart. / Schaefer, Saul; Ramasamy, R.; Lundmark, J. A.

In: FASEB Journal, Vol. 11, No. 3, 1997.

Research output: Contribution to journalArticle

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