Green Tea Catechin Normalizes the Enhanced Ca2+ Sensitivity of Myofilaments Regulated by a Hypertrophic Cardiomyopathy-Associated Mutation in Human Cardiac Troponin i (K206I)

Chad M. Warren, Chehade N. Karam, Beata M. Wolska, Tomoyoshi Kobayashi, Pieter P. De Tombe, Grace M. Arteaga, J. Martijn Bos, Michael J. Ackerman, R. John Solaro

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease characterized by thickening of ventricular walls and decreased left ventricular chamber volume. The majority of HCM-associated mutations are found in genes encoding sarcomere proteins. Herein, we set out to functionally characterize a novel HCMassociated mutation (K206I-TNNI3) and elucidate the mechanism of dysfunction at the level of myofilament proteins. Methods and Results-The male index case was diagnosed with HCM after an out-of-hospital cardiac arrest, which was followed by comprehensive clinical evaluation, transthoracic echocardiography, and clinical genetic testing. To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca2+ dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system comparing wild-type human troponin complex, 50% mix of K206I/wildtype, or 100% K206I. We also exchanged native troponin detergent extracted fibers with reconstituted troponin containing either wildtype or a 65% mix of K206I/wildtype and measured force generation. The Ca2+ sensitivity of the myofilaments containing the K206I variant was significantly increased, and when treated with 20 ìmol/L (-)-epigallocatechin gallate (green tea) was restored back to wild-type levels in ATPase and force measurements. The K206I mutation impairs the ability of the troponin I to inhibit ATPase activity in the absence of calcium-bound human cardiac troponin C. The ability of calcium-bound human cardiac troponin C to neutralize the inhibition of K206I was greater than with wild-type TnI. Conclusions-Compromised interactions of K206I with actin and hcTnC may lead to impaired relaxation and HCM.

Original languageEnglish (US)
Pages (from-to)765-773
Number of pages9
JournalCirculation: Cardiovascular Genetics
Issue number6
StatePublished - Dec 1 2015


  • Actin
  • actomyosin
  • calcium
  • echocardiography
  • troponin

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)


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