β-Adrenoceptor redistribution impairs NO/cGMP/PDE2 signalling in failing cardiomyocytes.
(2020) eLife — Vol. 9, p. e52221 [1-15] (2020)
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- Authors
Schobesberger, Sophie 
Wright, Peter T Gorelik, Julia
- Abstract
- Cardiomyocyte β-adrenoceptors (β-ARs) coupled to soluble guanylyl cyclase (sGC)-dependent production of the second messenger 3',5'-cyclic guanosine monophosphate (cGMP) have been shown to protect from heart failure. However, the exact localization of these receptors to fine membrane structures and subcellular compartmentation of β-AR/cGMP signals underpinning this protection in health and disease remain elusive. Here, we used a Förster Resonance Energy Transfer (FRET)-based cGMP biosensor combined with scanning ion conductance microscopy (SICM) to show that functional β-ARs are mostly confined to the T-tubules of healthy rat cardiomyocytes. Heart failure, induced via myocardial infarction, causes a decrease of the cGMP levels generated by these receptors and a change of subcellular cGMP compartmentation. Furthermore, attenuated cGMP signals led to impaired phosphodiesterase two dependent negative cGMP-to-cAMP cross-talk. In conclusion, topographic and functional reorganization of the β-AR/cGMP signalosome happens in heart failure and should be considered when designing new therapies acting via this receptor.
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Citations
Schobesberger, S., Wright, P. T., Poulet, C., Sanchez Alonso Mardones, J. L., Mansfield, C., Friebe, A., Harding, S. E., Balligand, J.-L., Nikolaev, V. O., & Gorelik, J. (2020). β-Adrenoceptor redistribution impairs NO/cGMP/PDE2 signalling in failing cardiomyocytes. eLife, 9, e52221 [1-15]. https://doi.org/10.7554/eLife.52221 (Original work published 2020)