A role for C‐protein in the regulation of contraction and intracellular Ca2+ in intact rat ventricular myocytes

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Abstract
1 C‐protein is a major component of muscle thick filaments whose function is unknown. We have examined for the first time the role of the regulatory binding domain of C‐protein in modulating contraction and intracellular Ca2+ concentration ([Ca2+]i) in intact cardiac myocytes. 2 Rat ventricular myocytes were reversibly permeabilised with the pore‐forming toxin streptolysin O. Myosin S2 (which binds to the regulatory domain of C‐protein) was introduced into cells during permeabilisation to compete with the endogenous C‐protein‐thick filament interaction. 3 Introduction of S2 into myocytes increased contractility by ∼30%, significantly lengthened the time to peak of the contraction and the time to half‐relaxation, but had no effect on [Ca2+]i transient amplitude. 4 Our data are consistent with increased myofilament Ca2+ sensitivity when there is reduced binding of C‐protein to myosin near the head‐tail junction. 5 We propose that the effects of introducing S2 into intact cardiac cells can be equated with the consequences of selectively phosphorylating C‐protein in vivo, and that the regulation of contraction by C‐protein is mediated by the effects of crossbridge cycling on the Ca2+ affinity of troponin C.