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Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium
Author(s) -
Fitzsimons Daniel P.,
Patel Jitandrakumar R.,
Moss Richard L.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.171by.x
Subject(s) - medicine , endocrinology , myocyte , myosin , chemistry , intracellular , stimulation , isoprenaline , biophysics , biology , biochemistry
1 The effects of ventricular myosin heavy chain (MHC) composition on the kinetics of activation and relaxation were examined in both chemically skinned and intact myocardial preparations from adult rats. Thyroid deficiency was induced to alter ventricular MHC isoform expression from ∼80 %α‐MHC/20 %β‐MHC in euthyroid rats to 100 %β‐MHC, without altering the expression of thin‐filament‐associated regulatory proteins. 2 In single skinned myocytes, increased expression of β‐MHC did not significantly affect either maximal Ca 2+ ‐activated tension ( P 0 ) or the Ca 2+ sensitivity of tension (pCa 50 ). However, unloaded shortening velocity ( V 0 ) decreased by 80 % due to increased β‐MHC expression. 3 The kinetics of activation and relaxation were examined in skinned multicellular preparations using the caged Ca 2+ compound DM‐nitrophen and caged Ca 2+ chelator diazo‐2, respectively. Myocardium expressing 100 %β‐MHC exhibited apparent rates of submaximal and maximal tension development ( k Ca ) that were 60 % lower than in control myocardium, and a 2‐fold increase in the half‐time for relaxation from steady‐state submaximal force. 4 The time courses of cell shortening and intracellular Ca 2+ transients were assessed in living, electrically paced myocytes, both with and without β‐adrenergic stimulation (70 n m isoproterenol (isoprenaline)). Thyroid deficiency had no affect on either the extent of myocyte shortening or the resting or peak fura‐2 fluorescence ratios. However, induction of β‐MHC expression by thyroid deficiency was associated with increased half‐times for myocyte shortening and relengthening and increased half‐time for the decay of the fura‐2 fluorescence ratio. Qualitatively similar results were obtained in both the absence and the presence of β‐adrenergic stimulation although the β‐agonist accelerated the kinetics of the twitch and the Ca 2+ transient. 5 Collectively, these data provide evidence that increased β‐MHC expression contributes significantly to the observed depression of contractile function in thyroid deficient myocardium by slowing the rates of both force development and force relaxation.