Mutations in Human Cardiac Troponin I That Are Associated with Restrictive Cardiomyopathy Affect Basal ATPase Activity and the Calcium Sensitivity of Force Development
Key result
Five cTnI mutations associated with restrictive cardiomyopathy showed increased Ca2+ sensitivity (deltapCa50 up to 0.47) and decreased ability to inhibit actomyosin ATPase activity versus wild-type.
Population
In vitro models studying human cardiac Troponin I mutations associated with restrictive cardiomyopathy
Comparison
Five cTnI mutations vs Wild-type cTnI
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Implicates altered troponin regulation in restrictive cardiomyopathy pathophysiology; leaves open translation to human phenotypes or therapies.
Structured PICO
P
Population
In vitro models (actomyosin ATPase and skinned fibers) studying human cardiac Troponin I (cTnI) mutations (L144Q, R145W, A171T, K178E, and R192H) associated with restrictive cardiomyopathy
I
Intervention
Five cTnI mutations (L144Q, R145W, A171T, K178E, and R192H)
C
Comparator
Wild-type cTnI
O
Outcome
Actomyosin ATPase activity and Ca2+ sensitivity of force developmentsurrogate
Mutations in cTnI associated with restrictive cardiomyopathy cause increased Ca2+ sensitivity and decreased ability to inhibit actomyosin ATPase activity, likely leading to severe diastolic dysfunction.
Cite This Study
Gomes et al. (2005) studied Restrictive cardiomyopathy. cTnI mutations (L144Q, R145W, A171T, K178E, and R192H) vs. Wild-type cTnI was evaluated on Ca2+ sensitivity of force development and actomyosin ATPase activity. Five cTnI mutations associated with restrictive cardiomyopathy showed increased Ca2+ sensitivity (deltapCa50 up to 0.47) and decreased ability to inhibit actomyosin ATPase activity versus wild-type.