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 C...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-02, Vol.301 (3), p.646-649
Main Authors: Bukatina, Anna E, Sieck, Gary C
Format: Article
Language:English
Subjects:
Activation
Animals
Cardiac muscle
Cardiotonic Agents - pharmacology
Cattle
Contraction
Culture Techniques
EMD 57033
Heart - drug effects
Heart - physiology
Myocardial Contraction - drug effects
Phalloidine - analogs & derivatives
Phalloidine - pharmacology
Quinolines - pharmacology
Regulation
Secophalloidin
Thiadiazines - pharmacology
Troponin I - metabolism
Vanadates - antagonists & inhibitors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 ∼30% increase in Ca 2+-independent force in muscles where Ca 2+ sensitivity was totally destroyed by troponin I extraction with 10 mM 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(03)00016-0