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J Neurosci. 1994 Jul;14(7):4226-36.

Modulation of skeletal muscle sodium channels in a satellite cell line by protein kinase C.

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  • 1Department of Pharmacology, University of Washington, Seattle, Washington 98195.

Abstract

Adult vertebrate skeletal muscle sodium channels are responsible for the spread of excitation from the end-plate through the muscle membrane and transverse tubular system that ultimately leads to contraction. These channels can be distinguished from other sodium channels by their sensitivity to both mu-conotoxin and TTX. The mouse satellite muscle cell line MM14 expresses only TTX- and mu-conotoxin-sensitive sodium channels having the physiological characteristics of adult skeletal muscle channels in both undifferentiated myoblasts and differentiated myotubes. Using undifferentiated and differentiated MM14 cells as well as primary cultures of rat skeletal muscle, we have examined modulation of adult skeletal muscle sodium channels by activators of protein kinase C (PKC). Stimulation of PKC by 1-oleoyl-2-acetyl-sn-glycerol (OAG) slows sodium current macroscopic inactivation rate by up to 70% and reduces the peak sodium current as much as 88%. Single-channel analysis reveals prolonged single channel openings and greatly increased probability of multiple channel openings during sustained depolarizations. These effects are due to PKC activation since they are blocked by a specific peptide inhibitor of PKC. The two effects of OAG are sequential. Low OAG concentrations can cause slowed macroscopic sodium current inactivation in the absence of peak current reduction, and intermediate concentrations of OAG cause slowing of inactivation followed by reduction of peak current. The separation of these two effects indicates that PKC modulation of the skeletal muscle sodium channel may occur by phosphorylation at two independent sites. PKC modulation of muscle sodium channels is expected to have important effects on muscle excitability and resultant contractile activity. Detection of adult skeletal muscle ion channels in replicating MM14 cells suggest that satellite cells may express a distinct subset of muscle-specific genes prior to activation of the terminal differentiation program.

PMID:
8027774
[PubMed - indexed for MEDLINE]
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