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

• Published in: The Journal of physiology Vol. 528; no. 1; pp. 151 - 156
• Main Authors: Calaghan, S. C., Trinick, J., Knight, P. J., White, E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01-10-2000; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Animals; Bacterial Proteins; Calcium - metabolism; Carrier Proteins; Cell Membrane Permeability - drug effects; Fluorescent Dyes; Fura-2; Heart Ventricles - cytology; Heart Ventricles - metabolism; In Vitro Techniques; Intracellular Fluid - metabolism; Male; Models, Cardiovascular; Muscle Proteins - metabolism; Muscle Proteins - pharmacology; Muscle, Skeletal - chemistry; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardium - cytology; Myocardium - metabolism; Myosin Subfragments - analysis; Rabbits; Rapid Report; Rats; Rats, Wistar; Rhodamines; Streptolysins - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2000.00151.x

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 Ca 2+ concentration ([Ca 2+ ] i ) in intact cardiac myocytes.
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.
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 [Ca 2+ ] i transient amplitude.
Our data are consistent with increased myofilament Ca 2+ sensitivity when there is reduced binding of C-protein to myosin near the head-tail junction.
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 Ca 2+ affinity of troponin C.