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Am J Physiol Cell Physiol 287: C270-C280, 2004. First published March 24, 2004; doi:10.1152/ajpcell.00015.2004
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12 skeletal muscle cells

Eva Zebedin,1 Walter Sandtner,1 Stefan Galler,2 Julia Szendroedi,1 Herwig Just,1 Hannes Todt,1 and Karlheinz Hilber1

1Institut für Pharmakologie, Medizinische Universität Wien, A-1090 Vienna; and 2Institut für Zoologie, Universität Salzburg, A-5020 Salzburg, Austria

Submitted 12 January 2004 ; accepted in final form 19 March 2004

Each skeletal muscle of the body contains a unique composition of "fast" and "slow" muscle fibers, each of which is specialized for certain challenges. This composition is not static, and the muscle fibers are capable of adapting their molecular composition by altered gene expression (i.e., fiber type conversion). Whereas changes in the expression of contractile proteins and metabolic enzymes in the course of fiber type conversion are well described, little is known about possible adaptations in the electrophysiological properties of skeletal muscle cells. Such adaptations may involve changes in the expression and/or function of ion channels. In this study, we investigated the effects of fast-to-slow fiber type conversion on currents via voltage-gated Na+ channels in the C2C12 murine skeletal muscle cell line. Prolonged treatment of cells with 25 nM of the Ca2+ ionophore A-23187 caused a significant shift in myosin heavy chain isoform expression from the fast toward the slow isoform, indicating fast-to-slow fiber type conversion. Moreover, Na+ current inactivation was significantly altered. Slow inactivation less strongly inhibited the Na+ currents of fast-to-slow fiber type-converted cells. Compared with control cells, the Na+ currents of converted cells were more resistant to block by tetrodotoxin, suggesting enhanced relative expression of the cardiac Na+ channel isoform Nav1.5 compared with the skeletal muscle isoform Nav1.4. These results imply that fast-to-slow fiber type conversion of skeletal muscle cells involves functional adaptation of their electrophysiological properties.

muscle plasticity; myosin heavy chain expression; sodium channel expression


Address for reprint requests and other correspondence: K. Hilber, Institut für Pharmakologie, Medizinische Universität Wien, Währinger Strasse 13A, A-1090 Vienna, Austria (E-mail: karlheinz.hilber{at}meduniwien.ac.at).




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