RGS3L allows for an M₂ muscarinic receptor-mediated RhoA-dependent inotropy in cardiomyocytes.

ABSTRACT: The role and outcome of the muscarinic M₂ acetylcholine receptor (M₂R) signaling in healthy and diseased cardiomyocytes is still a matter of debate. Here, we report that the long isoform of the regulator of G protein signaling 3 (RGS3L) functions as a switch in the muscarinic signaling, most likely of the M₂R, in primary cardiomyocytes. High levels of RGS3L, as found in heart failure, redirect the G_i-mediated Rac1 activation into a G_i-mediated RhoA/ROCK activation. Functionally, this switch resulted in a reduced production of reactive oxygen species (- 50%) in cardiomyocytes and an inotropic response (+ 18%) in transduced engineered heart tissues. Importantly, we could show that an adeno-associated virus 9-mediated overexpression of RG

SUBMITTER: Levay MK 

PROVIDER: S-EPMC8888479 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature