cAMP signaling affects age-associated deterioration of pacemaker beating interval dynamics.

Autor: Segal S; Laboratory of Bioelectric and Bioenegetic, The Faculty of Biomedical Engineering, Technion-IIT, Haifa, Israel., Shemla O; Laboratory of Bioelectric and Bioenegetic, The Faculty of Biomedical Engineering, Technion-IIT, Haifa, Israel., Shapira R; Laboratory of Bioelectric and Bioenegetic, The Faculty of Biomedical Engineering, Technion-IIT, Haifa, Israel., Peretz NK; Laboratory of Bioelectric and Bioenegetic, The Faculty of Biomedical Engineering, Technion-IIT, Haifa, Israel., Lukyanenko Y; Intramural Research Program, National Institute On Aging, Baltimore, MD, USA., Brosh I; Laboratory of Bioelectric and Bioenegetic, The Faculty of Biomedical Engineering, Technion-IIT, Haifa, Israel., Behar J; Laboratory of Bioelectric and Bioenegetic, The Faculty of Biomedical Engineering, Technion-IIT, Haifa, Israel., Lakatta EG; Intramural Research Program, National Institute On Aging, Baltimore, MD, USA., Tsutsui K; Intramural Research Program, National Institute On Aging, Baltimore, MD, USA. knt22e@gmail.com.; Department of Cardiovascular Medicine, Saitama Medical University International Medical Center, Saitama, Japan. knt22e@gmail.com., Yaniv Y; Laboratory of Bioelectric and Bioenegetic, The Faculty of Biomedical Engineering, Technion-IIT, Haifa, Israel. yaely@bm.technion.ac.il.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2023 Aug; Vol. 45 (4), pp. 2589-2600. Date of Electronic Publication: 2023 Apr 21.
DOI: 10.1007/s11357-023-00787-5
Abstrakt: Sinoatrial node (SAN) beating interval variability (BIV) and the average beating interval (BI) are regulated by a coupled-clock system, driven by Ca 2+ -calmodulin activated adenylyl cyclase, cAMP, and downstream PKA signaling. Reduced responsiveness of the BI and BIV to submaximal, [X] 50 , β-adrenergic receptor (β-AR) stimulation, and phosphodiesterase inhibition (PDEI) have been documented in aged SAN tissue, whereas the maximal responses, [X] max , do not differ by age. To determine whether age-associated dysfunction in cAMP signaling leads to altered responsiveness of BI and BIV, we measured cAMP levels and BI in adult (2-4 months n = 27) and aged (22-26 months n = 25) C57/BL6 mouse SAN tissue in control and in response to β-AR or PDEI at X 50 and [X] max . Both cAMP and average BI in adult SAN were reduced at X 50 , whereas cAMP and BI at X max did not differ by age. cAMP levels and average BI were correlated both within and between adult and aged SAN. BIV parameters in long- and short-range terms were correlated with cAMP levels for adult SAN. However, due to reduced cAMP within aged tissues at [X] 50 , these correlations were diminished in advanced age. Thus, cAMP level generated by the coupled clock mechanisms is tightly linked to average BI. Reduced cAMP level at X 50 in aged SAN explains the reduced responsiveness of the BI and BIV to β-AR stimulation and PDEI.
(© 2023. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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