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Myocardial energetics and redox in health and disease
014 Thin filaments reconstituted with troponin extracted from patients with hypertrophic obstructive cardiomyopathy are functionally abnormal
  1. C R Bayliss
  1. Imperial College, London, UK

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Tissue obtained from a septal myectomy represented an opportunity to characterise the molecular phenotype of hypertrophic obstructive cardiomyopathy (HOCM). We have isolated troponin from HOCM muscle and studied its function using the in-vitro motility assay (IVMA). The level of troponin I (TnI) phosphorylation has been measured as 0.29±0.04 mol Pi/mol TnI compared with 1.62±0.06 mol Pi/mol TnI in donor heart samples. The Ca2+-sensitivity of reconstituted thin filaments containing donor and HOCM troponin were measured. The HOCM troponin conferred a Ca2+-sensitivity that was not significantly different to that of the donor troponin. EC50 HOCM/donor=0.88±0.22 (n=8). HOCM troponin was treated with protein kinase A (PKA) (catalytic subunit) to increase the level of TnI phosphorylation to a similar level as found in donor hearts. There was no significant difference in the Ca2+ sensitivities of the thin filaments reconstituted with untreated or PKA-treated HOCM troponin. EC50 HOCM/PKA treated HOCM=0.93±0.32 (n=4). Finally, donor troponin was dephosphorylated by treatment with acid phosphatase. In preliminary experiments this was compared with HOCM troponin, which has an intrinsically low level of phosphorylation. Thin filaments reconstituted with dephosphorylated donor troponin had a higher Ca2+ sensitivity than thin filaments containing HOCM troponin. Therefore, we conclude that HOCM troponin is modified in a manner independent of the causative mutation. HOCM troponin confers a Ca2+ sensitivity similar to troponin from donor hearts, which is independent of the phosphorylation status of TnI. This molecular phenotype is different from both acquired heart failure and genetic dilated cardiomyopathy.

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