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Title: MONILIFORMIN - A CALCIUM CHANNEL BLOCKER?

Author
item NAGARAJ, R - UNIV OF WI
item WU, WEIDONG - UNIV OF WI
item WILL, J - UNIV OF WI
item VALDIVIA, H - UNIV OF WI
item LOKUTA, A - UNIV OF WI
item Vesonder, Ronald

Submitted to: Southern Poultry Science Society Meeting Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: 1/25/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: To understand the cellular mechanism of toxicity of moniliformin in chickens, several studies were conducted with isolated cardiac and skeletal muscles and microsomes. In experiments with isolated muscles, muscle strips were bathed in a Krebs-Henseleit solution (oxygenated with 95% O2 and 5% CO2) and equilibrated for over an hour, then incubated with moniliformin (MF) (80 uM) or water for 45 min. MF caused a significant reduction (P<.01) in contractile force within 5 min of incubation. In another set of experiments, after equilibration, the muscles were treated with 2.5 mM caffeine and further treated 5 min later with MF (80 uM) or water. MF was found to significantly prevent (P<.01) the reduction in contractile force which caffeine normally induces. Additionally, reconstitution of sarcoplasmic reticular (SR) Ca2+ channels in planar bilayers revealed that MF (8 uM) significantly decreased (P<.01) the open probability of the SR Ca2+ channels within 2 min of addition. Taken together, these results indicate that MF has a negative inotropic effect on striated muscle which could be due in part to an interaction between MF and the caffeine-sensitive ryanodine receptor.