Roles of Ca2+ and crossbridge kinetics in determining the maximum rates of Ca2+ activation and relaxation in rat and guinea pig skinned trabeculae.
We examined the influences of Ca2+ and crossbridge kinetics on the maximum rate of force development during Ca2+ activation of cardiac myofibrils and on the maximum rate of relaxation. Flash photolysis of diazo-2 or nitrophenyl-EGTA was used to produce a sudden decrease or increase, respectively, in [Ca2+] within Triton-skinned trabeculae from rat and guinea pig hearts (22 degrees C). Trabeculae from both species had similar Ca2+ sensitivities, suggesting that the rate of dissociation of Ca2+ from troponin C (k(off)) is similar in the 2 species. However, the rate of relaxation after diazo-2 photolysis was 5 times faster in the rat (16.1 +/- 0.9 s(-1), mean +/- SEM, n = 11) than in the guinea pig (2.99 +/- 0.26 s(-1), n = 7). This indicates that the maximum relaxation rate is limited by crossbridge kinetics rather than by k(off). The maximum rates of rapid activation by Ca2+ after nitrophenyl-EGTA photolysis (k(act)) and of force redevelopment after forcible crossbridge dissociation (k(act)) were similar and were approximately 5-fold faster in rat (k(act)= 14.4 +/- 0.9 s(-1), k(tr)= 13.0 +/- 0.6 s(-1)) than in guinea pig (k(act)= 2.57 +/- 0.14 s(-1), k(tr)= 2.69 +/- 0.30 s(-1)) trabeculae. This too may be mainly due to species differences in crossbridge kinetics. Both k(act) and k(tr) increased as [Ca2+] increased. This Ca2+ dependence of the rates of force development is consistent with current models for the Ca2+ activation of the crossbridge cycle, but these models do not explain the similarity in the maximal rates of activation and relaxation within a given species.
Department of Pharmacology, United Medical and Dental Schools, St. Thomas's Hospital, London, UK.
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Palmer
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Kentish
D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000528:radiation effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D017136:Ion Transport; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects*; D010782:Photolysis; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D019209:Troponin C / Q000378:metabolism*
D019209:Troponin C; C085112:2-nitrophenyl-EGTA; D004533:Egtazic Acid; D000205:Actomyosin; D002118:Calcium