Cardioprotection through a PKC-dependent decrease in myofilament ATPase

W. Glen Pyle, Yi Chen, Polly Hofmann

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Activation of myocardial κ-opioid receptor-protein kinase C (PKC) pathways may improve postischemic contractile function through a myofilament reduction in ATP utilization. To test this, we first examined the effects of PKC inhibitors on κ-opioid receptor-dependent cardioprotection. The κ-opioid receptor agonist U50,488H (U50) increased postischemic left ventricular developed pressure and reduced postischemic end-diastolic pressure compared with controls. PKC inhibitors abolished the cardioprotective effects of U50. To determine whether κ-opioid-PKC-dependent decreases in Ca 2+-dependent actomyosin Mg2+-ATPase could account for cardioprotection, we subjected hearts to three separate actomyosin ATPase-lowering protocols. We observed that moderate decreases in myofibrillar ATPase were equally cardioprotective as κ-opioid receptor stimulation. Immunoblot analysis and confocal microscopy revealed a κ-opioid-induced increase in myofilament-associated PKC-ε, and myofibrillar Ca 2+-independent PKC activity was increased after κ-opioid stimulation. This PKC-myofilament association led to an increase in troponin I and C-protein phosphorylation. Thus we propose PKC-ε activation and translocation to the myofilaments causes a decrease in actomyosin ATPase, which contributes to the κ-opioid receptor-dependent cardioprotective mechanism.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number3 54-3
StatePublished - Sep 1 2003

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Myofibrils
Protein Kinase C
Adenosine Triphosphatases
Opioid Receptors
Myosins
Opioid Analgesics
Protein C Inhibitor
Protein Kinase Inhibitors
Troponin C
Troponin I
Ventricular Pressure
Confocal Microscopy
Adenosine Triphosphate
Phosphorylation
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Cardioprotection through a PKC-dependent decrease in myofilament ATPase. / Pyle, W. Glen; Chen, Yi; Hofmann, Polly.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 3 54-3, 01.09.2003.

Research output: Contribution to journalArticle

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