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Am J Physiol Cell Physiol 285: C56-C63, 2003. First published February 26, 2003; doi:10.1152/ajpcell.00377.2002
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Ca2+ transients activate calcineurin/NFATc1 and initiate fast-to-slow transformation in a primary skeletal muscle culture

Hans-Peter Kubis, Nina Hanke, Renate J. Scheibe, Joachim D. Meissner, and Gerolf Gros

Zentrum Physiologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany

Submitted 20 August 2002 ; accepted in final form 11 February 2003

The calcineurin-mediated signal transduction via nuclear factor of activated T cells (NFATc1) is involved in upregulating slow myosin heavy chain (MHC) gene expression during fast-to-slow transformation of skeletal muscle cells. This study aims to investigate the Ca2+ signal necessary to activate the calcineurin-NFATc1 cascade in skeletal muscle. Electrostimulation of primary myocytes from rabbit for 24 h induced a distinct fast-to-slow transformation at the MHC mRNA level and a full activation of the calcineurin-NFATc1 pathway, although resting Ca2+ concentration ([Ca2+]i) remained unaltered at 70 nM. During activation, the calcium transients of these myocytes reach a peak concentration of ~500 nM. Although 70 nM [Ca2+]i does not activate calcineurin-NFAT, we show by the use of Ca2+ ionophore that the system is fully activated when [Ca2+]i is >=150 nM in a sustained manner. We conclude that the calcineurin signal transduction pathway and the slow MHC gene in cultured skeletal muscle cells are activated by repetition of the rapid high-amplitude calcium transients that are associated with excitation-contraction coupling rather than by a sustained elevation of resting Ca2+ concentration.

muscle plasticity; NFATc1; resting calcium concentration


Address for reprint requests and other correspondence: H.-P. Kubis, Zentrum Physiologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany, (E-mail: Kubis.HansP{at}mh-hannover.de).




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