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Differential effects of bepridil on functional properties of troponin C in slow and fast skeletal muscles
Author(s) -
Kischel P,
Stevens L,
Mounier Y
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702820
Subject(s) - bepridil , skeletal muscle , chemistry , differential (mechanical device) , neuroscience , medicine , biophysics , cardiology , biology , calcium , verapamil , engineering , aerospace engineering
Bepridil (BPD) is a pharmacological compound able to bind to the Ca 2+ sensor protein troponin C (TnC), which triggers skeletal muscle contraction upon Ca 2+ ‐binding. BPD can thereby modulate the Ca 2+ ‐affinity of this protein. The Ca 2+ ‐sensitizing action of bepridil was investigated on slow and fast isoforms of TnC from skinned slow and fast skeletal muscle fibres, activated by either Ca 2+ or Sr 2+ ions. Bepridil did not modify the Ca 2+ maximal tension of slow and fast fibres, suggesting that binding of the drug to TnC did not induce a change in the number of cross‐bridges involved in maximal tension. Sr 2+ ions induced lower maximal tension than Ca 2+ ions. However, in fast fibres, these lower Sr 2+ maximal tensions could be reinforced by bepridil, suggesting an effect of bepridil on the function of site I of fast TnC. Under submaximal tension, bepridil induced an increase in Ca 2+ affinity of TnC in both slow and fast fibres. However, slow fibres were more drug reactive than fast fibres, and the increase in tension appeared to be modulated by the Ca 2+ concentration. Thus, bepridil exerted a differential effect on slow and fast fibres. Moreover, the results suggest that bepridil was more effective when activation conditions were unfavourable.British Journal of Pharmacology (1999) 128 , 767–773; doi: 10.1038/sj.bjp.0702820