The relationship between contractile force and intracellular [Ca2+] in intact rat cardiac trabeculae

Peter H. Backx, Wei Dong Gao, Michelle D. Azan-Backx, Eduardo Marban

Research output: Contribution to journalArticle

Abstract

The control of force by [Ca2+] was investigated in rat cardiac trabeculae loaded with fura-2 salt. At sarcomere lengths of 2.1-2.3 µm, the steady state force-[Ca2+]i relationship during tetanization in the presence of ryanodine was half maximally activated at a [Ca2+]i of 0.65 ±. 0.19 µM with a Hill coefficient of 5.2 µ 1.2 (mean ± SD, n = 9), and the maximal stress produced at saturating [Ca2+]i equalled 121 ± 35 mN/mm 2 (n = 9). The dependence of steady state force on [Ca2+]i was identical in muscles tetanized in the presence of the Ca2+ATPase inhibitor cyclopiazonic acid (CPA). The force-[Ca2+]i relationship during the relaxation of twitches in the presence of CPA coincided exactly to that measured at steady state during tetani, suggesting that CPA slows the decay rate of [Ca2+]i sufficiently to allow the force to come into a steady state with the [Ca2+]i. In contrast, the relationship of force to [Ca2+]i during the relaxation phase of control twitches was shifted leftward relative to the steady state relationship, establishing that relaxation is limited by the contractile system itself, not by Ca2+ removal from the cytosol. Under control conditions the force-[Ca2+]i relationship, quantified at the time of peak twitch force (i.e., dF/dt = 0), coincided fairly well with steady state measurements in some trabeculae (i.e., three of seven). However, the force-[Ca2+]i relationship at peak force did not correspond to the steady state measurements after the application of 5 mM 2,3-butanedione monoxime (BDM) (to accelerate cross-bridge kinetics) or 100 µM CPA (to slow the relaxation of the [Ca2+]i transient). Therefore, we conclude that the relationship of force to [Ca2+]i during physiological twitch contractions cannot be used to predict the steady state relationship.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalJournal of General Physiology
Volume105
Issue number1
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Physiology

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