Universität zu Köln

Katnahji, Nour and Matthes, Jan ORCID: 0000-0003-2754-1555 (2025). Opposite effects of Gαi2 or Gαi3 deficiency on reduced basal density and attenuated β-adrenergic response of ventricular Ca2+ currents in myocytes of mice overexpressing the cardiac β1-adrenoceptor. Naunyn-Schmiedeberg's Archives of Pharmacology, 398 (9). pp. 12543-12549. Springer Nature. ISSN 0028-1298

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Abstract

Ca 2+ currents ( I CaL ) carried by ventricular L-type Ca 2+ channels (LTCC) are altered in failing hearts, and increased LTCC activity is discussed as a cause of cardiomyopathy. We have shown that lack of the inhibitory G-protein isoform Gα i3 improves cardiac outcome and survival in a murine heart-failure model of cardiac β 1 -adrenoceptor (β 1 -AR) overexpression (β 1 -tg), while lack of the Gα i2 isoform was detrimental in the same heart-failure model. Given the potential role of LTCC and their modulation by β-adrenergic signalling, we now analysed ventricular I CaL in β 1 -tg mice and in β 1 -tg mice lacking either Gα i2 or Gα i3 . Using the patch-clamp technique, we recorded whole-cell I CaL in ventricular myocytes freshly isolated from adult mice. Compared to age-matched wild-type littermates, basal I CaL was reduced in myocytes from β 1 -tg mice both under basal conditions (− 8.1 ± 1.6 vs. − 5.5 ± 1.5 pA/pF) and upon β-adrenergic stimulation with 1 µM isoproterenol (− 14.3 ± 5.6 vs. − 7.4 ± 1.9 pA/pF). Lack of Gα i3 normalised basal I CaL to nearly wild-type levels (− 7.5 ± 1.6 pA/pF), while β-adrenergic response remained attenuated (− 9.5 ± 3.6 pA/pF). In contrast, the absence of Gα i2 did not restore basal I CaL (− 5.7 ± 1.8 pA/pF), but restored the β-adrenergic response of I CaL , with the difference from basal current even exceeding that in wild-type mice (− 12.2 ± 2.9 pA/pF).We propose that by restoring basal I CaL , Gα i3 deficiency might contribute to the restoration of contractility in β 1 -tg mice, while maintaining attenuation of the I CaL response upon β-adrenergic stimulation protects against deleterious effects mediated by enhanced β-AR signalling. In contrast, restored and even enhanced I CaL response to β-adrenergic stimulation might contribute to detrimental effects of Gα i2 deficiency observed in β 1 -tg mice previously.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Katnahji, Nour UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthes, Jan UNSPECIFIED https://orcid.org/0000-0003-2754-1555 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-797996
Identification Number:	10.1007/s00210-025-03999-y
Journal or Publication Title:	Naunyn-Schmiedeberg's Archives of Pharmacology
Volume:	398
Number:	9
Page Range:	pp. 12543-12549
Number of Pages:	7
Date:	30 September 2025
Publisher:	Springer Nature
ISSN:	0028-1298
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Innere Medizin > Klinik II für Innere Medizin - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin Faculty of Medicine > Pharmakologie > Instítut für Pharmakologie
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79799