Ca2+ transients activate calcineurin/NFATc1 and initiate fast-to-slow transformation in a primary skeletal muscle culture.
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 approximately 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 >or=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.
Kubis
Hans-Peter
HP
Zentrum Physiologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany. Kubis.HansP@mh-hannover.de
Hanke
Nina
N
Scheibe
Renate J
RJ
Meissner
Joachim D
JD
Gros
Gerolf
G
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004558:Electric Stimulation; D015870:Gene Expression / Q000502:physiology; D007476:Ionophores / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000201:enzymology; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology / Q000201:enzymology; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000201:enzymology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011817:Rabbits; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D004268:DNA-Binding Proteins; D007476:Ionophores; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D000001:Calcimycin; D019703:Calcineurin; D018995:Myosin Heavy Chains; D002118:Calcium