title: Dimethyl sulphoxide enhances the effects of P(i) in myofibrils and inhibits the activity of rabbit skeletal muscle contractile proteins.
abstract: In the catalytic cycle of skeletal muscle, myosin alternates between strongly and weakly bound cross-bridges, with the latter contributing little to sustained tension. Here we describe the action of DMSO, an organic solvent that appears to increase the population of weakly bound cross-bridges that accumulate after the binding of ATP, but before P(i) release. DMSO (5-30%, v/v) reversibly inhibits tension and ATP hydrolysis in vertebrate skeletal muscle myofibrils, and decreases the speed of unregulated F-actin in an in vitro motility assay with heavy meromyosin. In solution, controls for enzyme activity and intrinsic tryptophan fluorescence of myosin subfragment 1 (S1) in the presence of different cations indicate that structural changes attributable to DMSO are small and reversible, and do not involve unfolding. Since DMSO depresses S1 and acto-S1 MgATPase activities in the same proportions, without altering acto-S1 affinity, the principal DMSO target apparently lies within the catalytic cycle rather than with actin-myosin binding. Inhibition by DMSO in myofibrils is the same in the presence or the absence of Ca(2+) and regulatory proteins, in contrast with the effects of ethylene glycol, and the Ca(2+) sensitivity of isometric tension is slightly decreased by DMSO. The apparent affinity for P(i) is enhanced markedly by DMSO (and to a lesser extent by ethylene glycol) in skinned fibres, suggesting that DMSO stabilizes cross-bridges that have ADP.P(i) or ATP bound to them.
authors.affiliation: Departamento de Bioquímica Médica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-590 RJ, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Mariano
authors.forename: G M
authors.initials: GM
authors.lastname: Alexandre
authors.forename: L C
authors.initials: LC
authors.lastname: Silva
authors.forename: A
authors.initials: A
authors.lastname: Romeiro
authors.forename: L C
authors.initials: LC
authors.lastname: Cameron
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: P B
authors.initials: PB
authors.lastname: Chase
authors.forename: M M
authors.initials: MM
authors.lastname: Sorenson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002645:Chickens; D003285:Contractile Proteins / Q000187:drug effects / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D019855:Ethylene Glycol / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009210:Myofibrils / Q000187:drug effects / Q000502:physiology*; D015879:Myosin Subfragments / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D003285:Contractile Proteins; D015879:Myosin Subfragments; D010710:Phosphates; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D000252:Calcium-Transporting ATPases; D019855:Ethylene Glycol; D008274:Magnesium; D002118:Calcium; D004121:Dimethyl Sulfoxide