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@article{Medvedev:2021:10.1038/s41598-021-84275-w,
author = {Medvedev, R and Sanchez, Alonso J and Mansfield, C and Judina, A and Francis, A and Pagiatakis, C and Trayanova, N and Glukhov, A and Miragoli, M and Faggian, G and Gorelik, J},
doi = {10.1038/s41598-021-84275-w},
journal = {Scientific Reports},
title = {Local hyperactivation of L-type Ca2+ channels increases spontaneous Ca2+ release activity and cellular hypertrophy in right ventricular myocytes from heart failure rats},
url = {http://dx.doi.org/10.1038/s41598-021-84275-w},
volume = {11},
year = {2021}
}

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TY - JOUR
AB - Right ventricle (RV) dysfunction is an independent predictor of patient survival in heart failure (HF). However, the mechanisms of RV progression towards failing are not well understood. We studied cellular mechanisms of RV remodelling in a rat model of left ventricle myocardial infarction (MI)-caused HF. RV myocytes from HF rats show significant cellular hypertrophy accompanied with a disruption of transverse-axial tubular network and surface flattening. Functionally these cells exhibit higher contractility with lower Ca2+ transients. The structural changes in HF RV myocytes correlate with more frequent spontaneous Ca2+ release activity than in control RV myocytes. This is accompanied by hyperactivated L-type Ca2+ channels (LTCCs) located specifically in the T-tubules of HF RV myocytes. The increased open probability of tubular LTCCs and Ca2+ sparks activation is linked to protein kinase A-mediated channel phosphorylation that occurs locally in T-tubules. Thus, our approach revealed that alterations in RV myocytes in heart failure are specifically localized in microdomains. Our findings may indicate the development of compensatory, though potentially arrhythmogenic, RV remodelling in the setting of LV failure. These data will foster better understanding of mechanisms of heart failure and it could promote an optimized treatment of patients.
AU - Medvedev,R
AU - Sanchez,Alonso J
AU - Mansfield,C
AU - Judina,A
AU - Francis,A
AU - Pagiatakis,C
AU - Trayanova,N
AU - Glukhov,A
AU - Miragoli,M
AU - Faggian,G
AU - Gorelik,J
DO - 10.1038/s41598-021-84275-w
PY - 2021///
SN - 2045-2322
TI - Local hyperactivation of L-type Ca2+ channels increases spontaneous Ca2+ release activity and cellular hypertrophy in right ventricular myocytes from heart failure rats
T2 - Scientific Reports
UR - http://dx.doi.org/10.1038/s41598-021-84275-w
UR - http://hdl.handle.net/10044/1/87158
VL - 11
ER -

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