© 1999 American Heart Association, Inc.
Original Contributions |
Effects of Myosin Heavy Chain Isoform Switching on Ca2+-Activated Tension Development in Single Adult Cardiac Myocytes
From the Department of Physiology, School of Medicine, University of Michigan, Ann Arbor, Mich.
Correspondence to Joseph M. Metzger, Department of Physiology, University of Michigan School of Medicine, 7730 Medical Science II, Ann Arbor, MI 48109-0622. E-mail metzgerj{at}umich.edu
Abstract—Cardiac myosin heavy
chain (MHC) isoforms are known to play a key role in defining the
dynamic contractile behavior of the heart during development. It
remains unclear, however, whether cardiac MHC isoforms influence other
important features of cardiac contractility, including
the Ca2+ sensitivity of isometric tension development. To
address this question, adult rats were treated chemically to induce the
hypothyroid state and cause a transition in the ventricular
cardiac MHC isoform expression pattern from predominantly the 
-MHC
isoform to exclusively the ß-MHC isoform. We found a significant
desensitization in the Ca2+ sensitivity of tension
development in ß-MHC–expressing ventricular myocytes
(pCa50=5.51±0.03, where pCa is –log[Ca2+],
and pCa50 is pCa at which tension is one-half maximal)
compared with that in predominantly -MHC–expressing myocytes
(pCa50=5.68±0.05). No differences between the 2 groups
were observed in the steepness of the tension-pCa relationship or in
the maximum isometric force generated. Instantaneous stiffness
measurements were made that provide a relative measure of changes in
the numbers of myosin crossbridges attached to actin during
Ca2+ activation. Results showed that the relative
stiffness-pCa relationship was shifted to the right in
ß-MHC–expressing myocytes compared with the -MHC–expressing
cardiac myocytes (pCa50=5.47±0.05 versus 5.76±0.05,
respectively). We conclude that MHC isoform switching in adult cardiac
myocytes alters the Ca2+ sensitivity of stiffness and
tension development. These results suggest that the activation
properties of the thin filament are in part MHC isoform dependent in
cardiac muscle, indicating an additional role for MHC isoforms in
defining cardiac contractile function.
Key Words: muscle contraction • Ca2+ • myosin
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