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Sphingomyelinase depresses force and calcium sensitivity of skeletal muscle contractile apparatus
Author(s) -
Ferreira Leonardo F.,
Moylan Jennifer S.,
Campbell Kenneth S.,
Reid Michael B.
Publication year - 2011
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.25.1_supplement.1059.19
Subject(s) - calcium , myofibril , sphingomyelin , chemistry , myosin , phosphorylation , biophysics , muscle contraction , medicine , biochemistry , endocrinology , biology , membrane , organic chemistry
Serum sphingomyelinase (SMase) activity is elevated in diseases that result in muscle weakness, e.g., heart failure. Exogenous SMase increases oxidants and depresses force in intact muscle by causing dysfunction in membrane excitability, calcium release, and/or the contractile apparatus. Our hypotheses were that SMase depresses force and calcium sensitivity of the contractile apparatus and promotes oxidation and phosphorylation of myofibrillar proteins. Mouse diaphragm fiber bundles were exposed to SMase (0.5 U/ml) or control (Krebs solution) for 60 min at 37°C. We used permeabilized single fibers to measure force and calcium‐sensitivity of the contractile apparatus. Carbonyl derivatives and Pro‐Q diamond staining were used as markers of protein oxidation and phosphorylation, respectively. SMase depressed maximal calcium‐activated force (in KN/m 2 : control 117 ± 6, SMase 93 ± 8; P < 0.05) and calcium sensitivity (pCa 50 : control 5.98 ± 0.03, SMase 5.91 ± 0.02; P < 0.05) of permeabilized single fibers. SMase increased myosin heavy chain (MHC) oxidation by 14 ± 0.2% ( P < 0.05), but did not affect myofibrillar protein phosphorylation. In conclusion, our data shows that SMase depresses force and calcium sensitivity of the contractile apparatus. The depression of maximal force may be explained, in part, by oxidation of MHC. *Funding provided by NIH (R01 AR055974 ; 1K99HLHL098453‐01) and AHA‐GRA (09POST2020082).