Secophalloidin as a novel activator of skinned cardiac muscle.
Secophalloidin (SPH) is known to activate skinned cardiac muscle in the absence of Ca(2+). We hypothesized that SPH-induced changes in cross-bridge properties underlie muscle activation. We found that force responsiveness to orthovanadate was drastically reduced in SPH activated muscles compared to Ca(2+)-activated contraction. Moreover, SPH caused approximately 30% increase in Ca(2+)-independent force in muscles where Ca(2+) sensitivity was totally destroyed by troponin I extraction with 10mM vanadate. Thus, SPH and Ca(2+) activation differ in both properties of the cross-bridge cycle and protein requirements for thin filament regulation. In addition, we tested the relationship between the activating effects SPH and EMD 57033, a Ca(2+) sensitizer that increases resting force in cardiac muscle. After maximal activation by either SPH or EMD 57033, the other compound was found to further increase force, indicating that SPH activates muscle via a novel mechanism.
Bukatina
Anna E
AE
Department of Physiology and Biophysics, Mayo Foundation, Rochester, MN 55905, USA. boukatina.anna@mayo.edu
Sieck
Gary C
GC
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002417:Cattle; D046508:Culture Techniques; D006321:Heart / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D010590:Phalloidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology; D019210:Troponin I / Q000378:metabolism; D014638:Vanadates / Q000037:antagonists & inhibitors
D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; D019210:Troponin I; C456940:secophalloidin-H-A; C070609:EMD 53998; D010590:Phalloidine; D014638:Vanadates