Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 302, Issue 12, Pages C1741-C1750Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00068.2012
Keywords
calcium ion influx; mechanosensitive channel; muscle regeneration; satellite cells; stretch-activation; voltage-gated channel
Categories
Funding
- NICHD
- Invitation Fellowship Programs for Research in Japan from the Japan Society for the Promotion of Science (JSPS)
- research grant of the Graduate School Student Projects Academic Challenge from the Entrepreneurship Center of Kyushu University
- funds from the Arizona Agriculture Experiment Station
- grants from the US Dept. of Agriculture National Research Initiative Competitive Grant [2005-35206-15255]
- Muscular Dystrophy Association Grant [MDA3685]
- funds from the Canadian Space Agency [9F007-52237-001-SR]
- Natural Sciences and Engineering Research Council [171302]
- scholarship from the Ministry of Education, Culture, Sports, Science and Technology-Japan (MEXT)
- [19380152]
- [22380145]
- Grants-in-Aid for Scientific Research [22580136, 22380145] Funding Source: KAKEN
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Hara M, Tabata K, Suzuki T, Do MQ, Mizunoya W, Nakamura M, Nishimura S, Tabata S, Ikeuchi Y, Sunagawa K, Anderson JE, Allen RE, Tatsumi R. Calcium influx through a possible coupling of cation channels impacts skeletal muscle satellite cell activation in response to mechanical stretch. Am J Physiol Cell Physiol 302: C1741-C1750, 2012. First published March 28, 2012; doi:10.1152/ajpcell.00068.2012.-When skeletal muscle is stretched or injured, satellite cells, resident myogenic stem cells positioned beneath the basal lamina of mature muscle fibers, are activated to enter the cell cycle. This signaling pathway is a cascade of events including calcium-calmodulin formation, nitric oxide (NO) radical production by NO synthase, matrix metalloproteinase activation, release of hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of HGF to the receptor c-met, as demonstrated by assays of primary cultures and in vivo experiments. Here, we add evidence that two ion channels, the mechanosensitive cation channel (MS channel) and the long-lasting-type voltage-gated calcium-ion channel (L-VGC channel), mediate the influx of extracellular calcium ions in response to cyclic stretch in satellite cell cultures. When applied to 1-h stretch cultures with individual inhibitors for MS and L-VGC channels (GsMTx-4 and nifedipine, respectively) or with a less specific inhibitor (gadolinium chloride, Gd), satellite cell activation and upstream HGF release were abolished, as revealed by bromodeoxyuridine-incorporation assays and Western blotting of conditioned media, respectively. The inhibition was dose dependent with a maximum at 0.1 mu M (GsMTx-4), 10 mu M (nifedipine), or 100 mu M (Gd) and canceled by addition of HGF to the culture media; a potent inhibitor for transient-type VGC channels (NNC55-0396, 100 mu M) did not show any significant inhibitory effect. The stretch response was also abolished when calcium-chelator EGTA (1.8 mM) was added to the medium, indicating the significance of extracellular free calcium ions in our present activation model. Finally, cation/calcium channel dependencies were further documented by calcium-imaging analyses on stretched cells; results clearly demonstrated that calcium ion influx was abolished by GsMTx-4, nifedipine, and EGTA. Therefore, these results provide an additional insight that calcium ions may flow in through L-VGC channels by possible coupling with adjacent MS channel gating that promotes the local depolarization of cell membranes to initiate the satellite cell activation cascade.
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