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Title: The effect of the PKC inhibitor calphostin C and the PKC agonist phorbol 12-myristate 13-acetate on regulation of cytosolic Ca{sup 2+} in mammalian skeletal muscle cells

Abstract

Protein kinase C (PKC) has been shown to exert broad actions in modulating Ca{sup 2+} in cardiac myocytes, however, the effect of PKC in skeletal muscle cells is largely unknown. In this study, we examined the effect of the PKC inhibitor calphostin C (CC) and the PKC agonist phorbol 12-myristate 13-acetate (PMA) on intracellular Ca{sup 2+} handling in C2C12 skeletal myotubes and skinned skeletal muscle fibers of the rat. CC (250 nM) significantly prolonged (P = 0.01, n = 6), and the PKC agonist PMA (500 nM; P = 0.03, n 6) significantly shortened the decay phase of electrically induced Ca{sup 2+} transients in C2C12 myotubes without affecting the amplitude or the time to peak of the transients. Skinned fiber studies showed that CC significantly inhibits SR Ca{sup 2+} uptake in skeletal muscle cells. PMA had no effect. CC also increased the peak of ATP-induced Ca{sup 2+} transients release by 94.2% (P < 0.0001) in the presence of extracellular Ca{sup 2+} and 54.5% (P = 0.04) without external Ca{sup 2+} via IP{sub 3}-Ca{sup 2+} release pathway in C2C12 myotubes, while PMA had no effect, suggesting that CC may modulate IP{sub 3}-induced Ca{sup 2+} release via a PKC-independent mechanism. CC atmore » a concentration of 1 {mu}M was able to induce a large sustained elevation in basal [Ca{sup 2+}]{sub i} that was blocked by Ca{sup 2+} store depletion and the IP{sub 3} receptor blocker 2-APB. These results indicate that PKC plays a role in modulation of SR function in skeletal muscle cells, and the PKC inhibitor CC may alter Ca{sup 2+} handling via both PKC-dependent and PKC-independent pathways.« less

Authors:
 [1];  [2]
  1. Physiology, School of Biomedical and Chemical Sciences, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 (Australia). E-mail: renzhi-han@uiowa.edu
  2. Physiology, School of Biomedical and Chemical Sciences, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 (Australia)
Publication Date:
OSTI Identifier:
20783471
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 212; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2005.07.023; PII: S0041-008X(05)00440-0; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; ATP; CALCIUM IONS; MUSCLES; RATS; RECEPTORS; SARCOPLASMIC RETICULUM; UPTAKE

Citation Formats

Han Renzhi, and Bakker, Anthony J. The effect of the PKC inhibitor calphostin C and the PKC agonist phorbol 12-myristate 13-acetate on regulation of cytosolic Ca{sup 2+} in mammalian skeletal muscle cells. United States: N. p., 2006. Web.
Han Renzhi, & Bakker, Anthony J. The effect of the PKC inhibitor calphostin C and the PKC agonist phorbol 12-myristate 13-acetate on regulation of cytosolic Ca{sup 2+} in mammalian skeletal muscle cells. United States.
Han Renzhi, and Bakker, Anthony J. Mon . "The effect of the PKC inhibitor calphostin C and the PKC agonist phorbol 12-myristate 13-acetate on regulation of cytosolic Ca{sup 2+} in mammalian skeletal muscle cells". United States. doi:.
@article{osti_20783471,
title = {The effect of the PKC inhibitor calphostin C and the PKC agonist phorbol 12-myristate 13-acetate on regulation of cytosolic Ca{sup 2+} in mammalian skeletal muscle cells},
author = {Han Renzhi and Bakker, Anthony J.},
abstractNote = {Protein kinase C (PKC) has been shown to exert broad actions in modulating Ca{sup 2+} in cardiac myocytes, however, the effect of PKC in skeletal muscle cells is largely unknown. In this study, we examined the effect of the PKC inhibitor calphostin C (CC) and the PKC agonist phorbol 12-myristate 13-acetate (PMA) on intracellular Ca{sup 2+} handling in C2C12 skeletal myotubes and skinned skeletal muscle fibers of the rat. CC (250 nM) significantly prolonged (P = 0.01, n = 6), and the PKC agonist PMA (500 nM; P = 0.03, n 6) significantly shortened the decay phase of electrically induced Ca{sup 2+} transients in C2C12 myotubes without affecting the amplitude or the time to peak of the transients. Skinned fiber studies showed that CC significantly inhibits SR Ca{sup 2+} uptake in skeletal muscle cells. PMA had no effect. CC also increased the peak of ATP-induced Ca{sup 2+} transients release by 94.2% (P < 0.0001) in the presence of extracellular Ca{sup 2+} and 54.5% (P = 0.04) without external Ca{sup 2+} via IP{sub 3}-Ca{sup 2+} release pathway in C2C12 myotubes, while PMA had no effect, suggesting that CC may modulate IP{sub 3}-induced Ca{sup 2+} release via a PKC-independent mechanism. CC at a concentration of 1 {mu}M was able to induce a large sustained elevation in basal [Ca{sup 2+}]{sub i} that was blocked by Ca{sup 2+} store depletion and the IP{sub 3} receptor blocker 2-APB. These results indicate that PKC plays a role in modulation of SR function in skeletal muscle cells, and the PKC inhibitor CC may alter Ca{sup 2+} handling via both PKC-dependent and PKC-independent pathways.},
doi = {},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 212,
place = {United States},
year = {Mon May 01 00:00:00 EDT 2006},
month = {Mon May 01 00:00:00 EDT 2006}
}