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Stretch‐like membrane permeabilization stimulates ERK2 phosphorylation dependent on calcium influx in C2C12 myotubes
Author(s) -
Rahnert Jill Anne,
Burkholder Thomas J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.962.17
Subject(s) - egta , calcium , microbiology and biotechnology , mapk/erk pathway , phosphorylation , chemistry , calcium in biology , myogenesis , intracellular , biophysics , myocyte , biochemistry , biology , organic chemistry
Mechanical stimulation of skeletal muscle is associated with hypertrophic signaling and increased membrane permeability. An increase in intracellular calcium may promote growth via ERK1/2 activation, and mechanical stretch may facilitate calcium influx either through stretch activated channels or by direct, physical damage of the membrane. These mechanisms differ in that, in addition to Ca 2+ influx, membrane damage would allow efflux of cytoplasmic proteins, which might activate ERK1/2 by calcium‐independent pathways. We hypothesize that calcium influx is sufficient to cause stretch‐induced ERK phosphorylation. C 2 C 12 cultures are treated with saponin to mimic membrane perforation or with A23187 to specifically facilitate calcium influx. In myotubes subjected to 15% mechanical stretch, ERK phosphorylation is increased to 161±45% (p=0.025) of control. Saponin treatment increases ERK phosphorylation to 489±290%, which is suppressed by 500uM EGTA. Similar to stretch, A23187 exposure increases ERK phosphorylation by 169±56% (p<0.001), but this is independent of EGTA. A23187 may also incorporate into intracellular membranes, and more complete calcium chelation with 5uM BAPTA‐AM completely blocked A23187 ‐induced ERK phosphorylation. We conclude that calcium entry is sufficient to stimulate activation of ERK implicating a role for calcium in initiating hypertrophic signaling.