The influence of 2,3-butanedione 2-monoxime (BDM) on the interaction between actin and myosin in solution and in skinned muscle fibres.
2,3-butanedione 2-monoxime (BDM) inhibits muscle contraction and actomyosin ATPase both in fibres and in solution. It is potentially useful as a tool for exploring weak interactions between actin and myosin. We have examined the effect of BDM on several key steps of the myosin subfragment-1 and actomyosin subfragment-1 ATPase in solution. These studies show that BDM shifts the equilibrium between two actomyosin states towards a more weakly bound form when the acto.myosin complex has ADP alone or ADP and phosphate bound. We also confirm the findings of Herrmann and colleagues (1993, Biochemistry, 31, 12227-32) that the main effect of BDM on the myosin subfragment-1 ATPase is to slow the release of phosphate following ATP hydrolysis. Skinned fibre studies show that the effects of BDM and phosphate on the steady isometric tension of the fibres are additive. This is consistent with the interpretation that BDM is reducing fibre tension either by increasing phosphate binding or by a direct effect on the crossbridge. Tension transients induced by rapid pressure release were examined in single muscle fibres; they showed that BDM reduces the rate of tension generation following pressure release. This result suggest that BDM directly affects the force generating event in the crossbridge.
McKillop
D F
DF
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
Fortune
N S
NS
Ranatunga
K W
KW
Geeves
M A
MA
D000199:Actins / Q000032:analysis* / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D015879:Myosin Subfragments / Q000032:analysis / Q000378:metabolism; D009218:Myosins / Q000032:analysis* / Q000378:metabolism*; D010710:Phosphates / Q000494:pharmacology; D011817:Rabbits
D000199:Actins; D002801:Cholinesterase Reactivators; D015879:Myosin Subfragments; D010710:Phosphates; C004717:diacetylmonoxime; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009218:Myosins; D003931:Diacetyl