T-tubule remodelling disturbs localized β2-adrenergic signalling in rat ventricular myocytes during the progression of heart failure

Schobesberger, S and Wright, P and Tokar, S and Bhargava, Anamika and Mansfield, C and Glukhov, A V and Poulet, C and Buzuk, A and Monszpart, A and Sikkel, M and Harding, S E and Nikolaev, V O and Lyon, A R and Gorelik, J (2017) T-tubule remodelling disturbs localized β2-adrenergic signalling in rat ventricular myocytes during the progression of heart failure. Cardiovascular Research, 113 (7). pp. 770-782. ISSN 0008-6363

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Abstract

Cardiomyocyte β2-adrenergic receptor (β2AR) cyclic adenosine monophosphate (cAMP) signalling is regulated by the receptors’ subcellular location within transverse tubules (T-tubules), via interaction with structural and regulatory proteins, which form a signalosome. In chronic heart failure (HF), β2ARs redistribute from T-tubules to the cell surface, which disrupts functional signalosomes and leads to diffuse cAMP signalling. However, the functional consequences of structural changes upon β2AR-cAMP signalling during progression from hypertrophy to advanced HF are unknown.

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