Publications

BibTex format

@article{Wright:2018:10.3389/fphys.2018.01302,
author = {Wright, PT and Sanchez-Alonso, JL and Lucarelli, C and Alvarez-Laviada, A and Poulet, CE and Bello, SO and Faggian, G and Terracciano, CM and Gorelik, J},
doi = {10.3389/fphys.2018.01302},
journal = {Frontiers in Physiology},
title = {Partial mechanical unloading of the heart disrupts L-type calcium channel and beta-adrenoceptor signaling microdomains},
url = {http://dx.doi.org/10.3389/fphys.2018.01302},
volume = {9},
year = {2018}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Introduction: We investigated the effect of partial mechanical unloading (PMU) of the heart on the physiology of calcium and beta-adrenoceptor-cAMP (βAR-cAMP) microdomains. Previous studies have investigated PMU using a model of heterotopic-heart and lung transplantation (HTHAL). These studies have demonstrated that PMU disrupts the structure of cardiomyocytes and calcium handling. We sought to understand these processes by studying L-Type Calcium Channel (LTCC) activity and sub-type-specific βAR-cAMP signaling within cardiomyocyte membrane microdomains.Method: We utilized an 8-week model of HTHAL, whereby the hearts of syngeneic Lewis rats were transplanted into the abdomens of randomly assigned cage mates. A pronounced atrophy was observed in hearts after HTHAL. Cardiomyocytes were isolated via enzymatic perfusion. We utilized Förster Resonance Energy Transfer (FRET) based cAMP-biosensors and scanning ion conductance microscopy (SICM) based methodologies to study localization of LTCC and βAR-cAMP signaling.Results: β2AR-cAMP responses measured by FRET in the cardiomyocyte cytosol were reduced by PMU (loaded 28.51 ± 7.18% vs. unloaded 10.84 ± 3.27% N,n 4/10-13 mean ± SEM ∗p < 0.05). There was no effect of PMU on β2AR-cAMP signaling in RII_Protein Kinase A domains. β1AR-cAMP was unaffected by PMU in either microdomain. Consistent with this SICM/FRET analysis demonstrated that β2AR-cAMP was specifically reduced in t-tubules (TTs) after PMU (loaded TT 0.721 ± 0.106% vs. loaded crest 0.104 ± 0.062%, unloaded TT 0.112 ± 0.072% vs. unloaded crest 0.219 ± 0.084% N,n 5/6-9 mean ± SEM ∗∗p < 0.01, ∗∗∗p < 0.001 vs. loaded TT). By comparison β1AR-cAMP responses in either TT or sarcolemmal crests were unaffected by the PMU. LTCC occurrence and open probability (Po) were reduced by PMU (loaded TT Po 0.073 ± 0.011% vs. load
AU  - Wright,PT
AU  - Sanchez-Alonso,JL
AU  - Lucarelli,C
AU  - Alvarez-Laviada,A
AU  - Poulet,CE
AU  - Bello,SO
AU  - Faggian,G
AU  - Terracciano,CM
AU  - Gorelik,J
DO  - 10.3389/fphys.2018.01302
PY  - 2018///
SN  - 1664-042X
TI  - Partial mechanical unloading of the heart disrupts L-type calcium channel and beta-adrenoceptor signaling microdomains
T2  - Frontiers in Physiology
UR  - http://dx.doi.org/10.3389/fphys.2018.01302
UR  - http://hdl.handle.net/10044/1/63953
VL  - 9
ER  -

Download

ProfessorCesareTerracciano

Contact

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)