title: Effects of troponin-I extraction with vanadate and of the calcium sensitizer EMD 53998 on the rate of force generation in skinned cardiac muscle.
abstract: The rate of tension development following release of ATP from caged-ATP in the presence of calcium was studied in skinned cardiac fibres from swine. A low-force rigor state was obtained by using butanedione monoxime (BDM) during the induction of rigor. BDM was washed out and following release of ATP in the presence of Ca2+ (pCa 4.3), the muscles contracted with an apparent rate of about 2 s-1 at 22 degrees C. After treatment with 10 mM vanadate to extract troponins I and C the fibres contracted independently of calcium. The rate of contraction upon release of ATP was slower than prior to extraction and was independent of [Ca2+]. Since treatment with vanadate has been shown to extract about 90% of troponin-I the results suggest that the muscles under these conditions are partially activated by removal of an inhibition of cross-bridge interaction by troponin I. A partial recovery of force was obtained by prolonged incubation in DTT containing solutions possibly reflecting reconstitution with troponin I still present in the fibre bundle. Treatment with a solution containing whole troponin caused almost complete recovery of calcium sensitivity and rate of force development. The calcium sensitizer EMD 53998 increased rates of contraction in a dose dependent manner, suggesting that this compound increases force and calcium sensitivity by increasing the cross-bridge attachment rates.
authors.affiliation: Department of Physiology and Biophysics, Lund University, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Arner
authors.forename: J D
authors.initials: JD
authors.lastname: Strauss
authors.forename: C
authors.initials: C
authors.lastname: Svensson
authors.forename: J C
authors.initials: JC
authors.lastname: Rüegg
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010782:Photolysis; D011804:Quinolines / Q000494:pharmacology*; D013552:Swine; D013829:Thiadiazines / Q000494:pharmacology*; D013997:Time Factors; D014336:Troponin / Q000302:isolation & purification / Q000502:physiology*; D019210:Troponin I; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; D014336:Troponin; D019210:Troponin I; C070609:EMD 53998; D014638:Vanadates; C029273:P(3)-1-(2-nitro)phenylethyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D002118:Calcium