Increased Myocyte Calcium Sensitivity in End-Stage Pediatric Dilated Cardiomyopathy.

Increased Myocyte Calcium Sensitivity in End-Stage Pediatric Dilated Cardiomyopathy. Am J Physiol Heart Circ Physiol. 2019 Oct 18;: Authors: Nakano SJ, Walker JS, Walker LA, Li X, Du Y, Miyamoto SD, Sucharov CC, Garcia AM, Mitchell MB, Ambardekar AV, Stauffer BL Abstract Dilated cardiomyopathy (DCM) is the most common cause of heart failure (HF) in children, resulting in high mortality and need for heart transplantation. The pathophysiology underlying pediatric DCM is largely unclear, however there is emerging evidence that molecular adaptations and response to conventional HF medications differ between children and adults. In order to gain insight into alterations leading to systolic dysfunction in pediatric DCM, we measured cardiomyocyte contractile properties and sarcomeric protein phosphorylation in explanted pediatric DCM myocardium (N=8) compared to non-failing (NF) pediatric hearts (N=8). Force-pCa curves were generated from skinned cardiomyocytes, in the presence and absence of protein kinase A (PKA). Sarcomeric protein phosphorylation was quantified using ProQ Diamond staining following gel electrophoresis. Pediatric DCM cardiomyocytes demonstrate increased calcium sensitivity (pCa50 = 5.70 ± 0.0291) with an associated decrease in troponin I (TnI) phosphorylation when compared to NF pediatric cardiomyocytes (pCa50 = 5.59 ± 0.0271, p=0.0073). Myosin binding protein C (MBPC) and troponin T (TnT) phosphorylation are also lowe...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research