Calcium-independent activation of skinned cardiac muscle by secophalloidin

• Published in: FEBS letters Vol. 519; no. 1; pp. 201 - 204
• Main Authors: Bukatina, Anna E, Theodore, Lou J, Campbell, Kenneth B, Sieck, Gary C
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 22.05.2002
• Subjects: Actins - metabolism; Activation; Animals; BDM, 2,3-butanedione monoxime; Calcium - metabolism; Cardiac muscle; Cattle; CDTA, trans-1,2-cyclohexanediamine-N,N,N′,N′-tetraacetic acid; Contraction; Heart Ventricles - drug effects; Heart Ventricles - metabolism; In Vitro Techniques; Isometric Contraction - drug effects; Myocardial Contraction - drug effects; Myocardium - metabolism; Phalloidine - analogs & derivatives; Phalloidine - chemistry; Phalloidine - pharmacology; Regulation; Secophalloidin; SPH, secophalloidin; SPH-H-A, secophalloidin hydroxy acid; SPH-L, secophalloidin lactone; Stress, Mechanical; Structure-Activity Relationship; TnC, troponin C; Troponin C - chemistry; Troponin C - metabolism; SPH-H-A, secophalloidin hydroxy acid; Secophalloidin; Cardiac muscle; SPH-L, secophalloidin lactone; CDTA, trans-1,2-cyclohexanediamine- N, N, N′, N′-tetraacetic acid; SPH, secophalloidin; TnC, troponin C; Activation; Regulation; BDM, 2,3-butanedione monoxime; Contraction
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02766-7

Thin filament regulation of muscle contraction is believed to be mediated by both Ca 2+ and strongly bound myosin cross-bridges. We found that secophalloidin (SPH, 5–8 mM) activates cross-bridge cycling without Ca 2+ causing isometric force comparable to that induced by Ca 2+. At saturated [SPH], Ca 2+ further increased force by 20%. SPH-induced force was reversible upon washing with a relaxing solution. However, there was more than 30% irreversible loss in subsequent Ca 2+-activated force. We hypothesize that SPH activates muscle via strongly bound cross-bridges. SPH-activated contraction provides a new model for studying the role of Ca 2+ and cross-bridges in muscle regulation.