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CALL FOR PAPERS: Comparative genomics

Increasing mammalian cardiomyocyte contractility with residues identified in trout troponin C

¹ Department of Bioengineering, University of Washington, Seattle, Washington
² Cardiovascular Sciences, BC Research Institute for Children and Women's Health, Vancouver, British Columbia, Canada
³ Cardiac Membrane Research Lab, Simon Fraser University, Burnaby, British Columbia, Canada

The Ca²⁺ sensitivity of force generation in trout cardiac myocytes is significantly greater than that from mammalian hearts. One mechanism that we have suggested to be responsible, at least in part, for this high Ca²⁺ sensitivity is the isoform of cardiac troponin C (cTnC) found in trout hearts (ScTnC), which has greater than twice the Ca²⁺ affinity of mammalian cTnC (McTnC). Here, through a series of mutations, the residues in ScTnC responsible for its high Ca²⁺ affinity have been identified as being Asn², Ile²⁸, Gln²⁹, and Asp³⁰. When these residues in McTnC were mutated to the trout-equivalent amino acid, the Ca²⁺ affinity of the molecule, determined by monitoring the fluorescence of a Trp inserted for a Phe at residue 27, is comparable to that of ScTnC. To determine how a McTnC mutant containing Asn², Ile²⁸, Gln²⁹, and Asp³⁰ (NIQD McTnC) affects the Ca²⁺ sensitivity of force generation, endogenous cTnC in single, chemically skinned rabbit cardiomyocytes was replaced with either wild-type McTnC or NIQD McTnC. Our results demonstrate that the cardiomyocytes containing NIQD McTnC were approximately twice as sensitive to Ca²⁺, illustrating that a McTnC mutant with similar Ca²⁺ affinity as ScTnC can be used to sensitize mammalian cardiac myocytes to Ca²⁺.

temperature; cardiac contractility; cold adaptation of proteins; Ca²⁺ affinity

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				B. Liang, F. Chung, Y. Qu, D. Pavlov, T. E. Gillis, S. B. Tikunova, J. P. Davis, and G. F. Tibbits Familial hypertrophic cardiomyopathy-related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility Physiol Genomics, April 1, 2008; 33(2): 257 - 266. [Abstract] [Full Text] [PDF]

				T. E. Gillis, C. R. Marshall, and G. F. Tibbits Functional and evolutionary relationships of troponin C Physiol Genomics, December 19, 2007; 32(1): 16 - 27. [Abstract] [Full Text] [PDF]

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