Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts

Peter T Wright; Navneet K Bhogal; Ivan Diakonov; Laura M K Pannell; Ruwan K Perera; Nadja I Bork; Sophie Schobesberger; Carla Lucarelli; Giuseppe Faggian; Anita Alvarez-Laviada; Manuela Zaccolo; Timothy J Kamp; Ravi C Balijepalli; Alexander R Lyon; Sian E Harding; Viacheslav O Nikolaev; Julia Gorelik

doi:10.1016/j.celrep.2018.03.053

Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts

Standard

Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts. / Wright, Peter T; Bhogal, Navneet K; Diakonov, Ivan; Pannell, Laura M K; Perera, Ruwan K; Bork, Nadja I; Schobesberger, Sophie; Lucarelli, Carla; Faggian, Giuseppe; Alvarez-Laviada, Anita; Zaccolo, Manuela; Kamp, Timothy J; Balijepalli, Ravi C; Lyon, Alexander R; Harding, Sian E; Nikolaev, Viacheslav O; Gorelik, Julia.

in: CELL REP, Jahrgang 23, Nr. 2, 10.04.2018, S. 459-469.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wright, PT, Bhogal, NK, Diakonov, I, Pannell, LMK, Perera, RK, Bork, NI, Schobesberger, S, Lucarelli, C, Faggian, G, Alvarez-Laviada, A, Zaccolo, M, Kamp, TJ, Balijepalli, RC, Lyon, AR, Harding, SE, Nikolaev, VO & Gorelik, J 2018, 'Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts', CELL REP, Jg. 23, Nr. 2, S. 459-469. https://doi.org/10.1016/j.celrep.2018.03.053

APA

Wright, P. T., Bhogal, N. K., Diakonov, I., Pannell, L. M. K., Perera, R. K., Bork, N. I., Schobesberger, S., Lucarelli, C., Faggian, G., Alvarez-Laviada, A., Zaccolo, M., Kamp, T. J., Balijepalli, R. C., Lyon, A. R., Harding, S. E., Nikolaev, V. O., & Gorelik, J. (2018). Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts. CELL REP, 23(2), 459-469. https://doi.org/10.1016/j.celrep.2018.03.053

Vancouver

Wright PT, Bhogal NK, Diakonov I, Pannell LMK, Perera RK, Bork NI et al. Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts. CELL REP. 2018 Apr 10;23(2):459-469. https://doi.org/10.1016/j.celrep.2018.03.053

Bibtex

@article{86ff99b3f52a40ddae496161f93e2fb0,

title = "Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts",

abstract = "Cardiomyocytes from the apex but not the base of the heart increase their contractility in response to β2-adrenoceptor (β2AR) stimulation, which may underlie the development of Takotsubo cardiomyopathy. However, both cell types produce comparable cytosolic amounts of the second messenger cAMP. We investigated this discrepancy using nanoscale imaging techniques and found that, structurally, basal cardiomyocytes have more organized membranes (higher T-tubular and caveolar densities). Local membrane microdomain responses measured in isolated basal cardiomyocytes or in whole hearts revealed significantly smaller and more short-lived β2AR/cAMP signals. Inhibition of PDE4, caveolar disruption by removing cholesterol or genetic deletion of Cav3 eliminated differences in local cAMP production and equilibrated the contractile response to β2AR. We conclude that basal cells possess tighter control of cAMP because of a higher degree of signaling microdomain organization. This provides varying levels of nanostructural control for cAMP-mediated functional effects that orchestrate macroscopic, regional physiological differences within the heart.",

keywords = "Journal Article",

author = "Wright, {Peter T} and Bhogal, {Navneet K} and Ivan Diakonov and Pannell, {Laura M K} and Perera, {Ruwan K} and Bork, {Nadja I} and Sophie Schobesberger and Carla Lucarelli and Giuseppe Faggian and Anita Alvarez-Laviada and Manuela Zaccolo and Kamp, {Timothy J} and Balijepalli, {Ravi C} and Lyon, {Alexander R} and Harding, {Sian E} and Nikolaev, {Viacheslav O} and Julia Gorelik",

year = "2018",

month = apr,

day = "10",

doi = "10.1016/j.celrep.2018.03.053",

language = "English",

volume = "23",

pages = "459--469",

journal = "CELL REP",

issn = "2211-1247",

publisher = "Elsevier",

number = "2",

}

RIS

TY - JOUR

T1 - Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βAR-cAMP Responsiveness in Murine Hearts

AU - Wright, Peter T

AU - Bhogal, Navneet K

AU - Diakonov, Ivan

AU - Pannell, Laura M K

AU - Perera, Ruwan K

AU - Bork, Nadja I

AU - Schobesberger, Sophie

AU - Lucarelli, Carla

AU - Faggian, Giuseppe

AU - Alvarez-Laviada, Anita

AU - Zaccolo, Manuela

AU - Kamp, Timothy J

AU - Balijepalli, Ravi C

AU - Lyon, Alexander R

AU - Harding, Sian E

AU - Nikolaev, Viacheslav O

AU - Gorelik, Julia

PY - 2018/4/10

Y1 - 2018/4/10

N2 - Cardiomyocytes from the apex but not the base of the heart increase their contractility in response to β2-adrenoceptor (β2AR) stimulation, which may underlie the development of Takotsubo cardiomyopathy. However, both cell types produce comparable cytosolic amounts of the second messenger cAMP. We investigated this discrepancy using nanoscale imaging techniques and found that, structurally, basal cardiomyocytes have more organized membranes (higher T-tubular and caveolar densities). Local membrane microdomain responses measured in isolated basal cardiomyocytes or in whole hearts revealed significantly smaller and more short-lived β2AR/cAMP signals. Inhibition of PDE4, caveolar disruption by removing cholesterol or genetic deletion of Cav3 eliminated differences in local cAMP production and equilibrated the contractile response to β2AR. We conclude that basal cells possess tighter control of cAMP because of a higher degree of signaling microdomain organization. This provides varying levels of nanostructural control for cAMP-mediated functional effects that orchestrate macroscopic, regional physiological differences within the heart.

AB - Cardiomyocytes from the apex but not the base of the heart increase their contractility in response to β2-adrenoceptor (β2AR) stimulation, which may underlie the development of Takotsubo cardiomyopathy. However, both cell types produce comparable cytosolic amounts of the second messenger cAMP. We investigated this discrepancy using nanoscale imaging techniques and found that, structurally, basal cardiomyocytes have more organized membranes (higher T-tubular and caveolar densities). Local membrane microdomain responses measured in isolated basal cardiomyocytes or in whole hearts revealed significantly smaller and more short-lived β2AR/cAMP signals. Inhibition of PDE4, caveolar disruption by removing cholesterol or genetic deletion of Cav3 eliminated differences in local cAMP production and equilibrated the contractile response to β2AR. We conclude that basal cells possess tighter control of cAMP because of a higher degree of signaling microdomain organization. This provides varying levels of nanostructural control for cAMP-mediated functional effects that orchestrate macroscopic, regional physiological differences within the heart.

KW - Journal Article

U2 - 10.1016/j.celrep.2018.03.053

DO - 10.1016/j.celrep.2018.03.053

M3 - SCORING: Journal article

C2 - 29642004

VL - 23

SP - 459

EP - 469

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 2

ER -