Journal article
Molecular mechanisms of cardiac myofilament activation: modulation by pH and a troponin T mutant R92Q
Basic research in cardiology, Vol.97 Suppl 1(S1), pp.I102-I110
2002
Handle:
https://hdl.handle.net/2376/115519
PMID: 12479243
Abstract
Activation of cardiac myofilaments is a complex process involving steric, allosteric, and cooperative mechanisms. The complexity of the protein-protein interactions that result in the rise and fall of tension in the heartbeat provide many points that may be modified by various control mechanisms. These include modulation by the sarcomere length, covalent modulation by protein phosphorylation and non-covalent modulation by the chemical environment surrounding the myofilaments. We focus here on effects of pH change in the context of one of the mutations in cardiac troponin T (R92Q) that causes familial hypertrophic cardiomyopathy (FHC). We tested whether this change in charge would manifest itself functionally by a difference in the pCa-force relations of skinned fiber bundles activated at pH values of 6.5, 7.0 and 7.5. Fiber bundles containing the cTnT-R92Q mutant demonstrated an increase in sensitivity to Ca2+ at all three pH values. However, the relative magnitude of the increase in Ca2+-sensitivity induced by the mutant cTnT increased as the pH was decreased from pH 7.5 to pH 7.0 and to pH 6.5. Maximum force generated by the myofilaments fell as pH was lowered over this range, but the percent fall in maximum force was the same for fiber bundles containing wild-type and mutant cTnT. Our results indicate that ischemia that may be associated with FHC may exacerbate the functional changes induced by the cTnT mutation.
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Details
- Title
- Molecular mechanisms of cardiac myofilament activation: modulation by pH and a troponin T mutant R92Q
- Creators
- R John Solaro - Department of Physiology and Biophysics (M/C 901), College of Medicine, University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612-7342, USA. SolaroRJ@uic.eduJamie VargheseA J MarianMurali Chandra
- Publication Details
- Basic research in cardiology, Vol.97 Suppl 1(S1), pp.I102-I110
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Germany
- Grant note
- R01 HL068884-02 / NHLBI NIH HHS P50 HL054313-060012 / NHLBI NIH HHS R01 HL068884-05 / NHLBI NIH HHS P50 HL054313-090012 / NHLBI NIH HHS R01 HL068884-01 / NHLBI NIH HHS P50 HL054313-100012 / NHLBI NIH HHS R01 HL068884 / NHLBI NIH HHS P50 HL054313-080012 / NHLBI NIH HHS P50 HL054313 / NHLBI NIH HHS P50 HL054313-08S10012 / NHLBI NIH HHS R01 HL068884-04 / NHLBI NIH HHS P50 HL054313-070012 / NHLBI NIH HHS R01 HL068884-03 / NHLBI NIH HHS
- Identifiers
- 99900547772201842
- Language
- English
- Resource Type
- Journal article