Characterization of secophalloidin-induced force loss in cardiac myofibrils.
Secophalloidin (SPH) is known to cause in cardiac myofibrils force without Ca(2+) (half-maximal effect approximately 2 mM) followed by irreversible loss of Ca(2+)-activated force. At maximal Ca(2+) activation, SPH increases force (half-maximal effect < 0.1 mM). We found that SPH at low concentration (0.5 mM) did not cause either force activation or force loss at pCa 8.7, but both of these effects did occur when force was activated by Ca(2+). The force loss was prevented when SPH was applied during rigor or in the presence of 2,3-butanedione monoxime (85 mM). Furthermore, studying muscle in which the force was previously reduced by SPH (up to 50%) did not reveal significant changes in Ca(2+) sensitivity and cooperativity of Ca(2+) activation or qualitative alterations in SPH-induced changes in Ca(2+)-activated contraction. Data suggest that the force loss is mediated by cycling cross-bridges, and might reflect a reduction in force generated by individual cross-bridges.
Bukatina
Anna E
AE
Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA. boukatina.anna@mayo.edu
Sieck
Gary C
GC
Campbell
Kenneth B
KB
Belohlavek
Marek
M
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D018908:Muscle Weakness / Q000139:chemically induced* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D009218:Myosins / Q000187:drug effects / Q000502:physiology; D010590:Phalloidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D034421:Sus scrofa
C456940:secophalloidin-H-A; D010590:Phalloidine; D000255:Adenosine Triphosphate; D009218:Myosins; D002118:Calcium