Aging-induced down-regulation of PKA/BKCa pathway in rat cerebral arteries

Title:

Aging-induced down-regulation of PKA/BKCa pathway in rat cerebral arteries

Creator:

Li, Na, Shi, Ruixiu, Ye, Yang, Zhang, Yingying, Zhang, Yumeng, Wang, Zhizhi, Gu, Ying, Yin, Yongxiang, Chen, Daozhen, and Tang, Jiaqi

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:df104907-bc71-4084-95d9-4a86e7c53971
uuid:df104907-bc71-4084-95d9-4a86e7c53971
doi:10.33549/physiolres.934944

Subject:

cerebral artery, large-conductance Ca2+-activated-K+ channel, aging, vessel dilatation, and protein kinase A

Type:

model:article and TEXT

Format:

počítač and online zdroj

Description:

The incidence of cerebrovascular diseases increases significantly with aging. This study aimed to test the hypothesis that aging may influence the protein kinase A (PKA)-dependent vasodilation via RyR/BKCa pathway in the middle cerebral arteries (MCA). Male Sprague-Dawley rats were randomly divided into control (4-6 month-old) and aged (24-month-old) groups. The functions of MCA and ion channel activities in smooth muscle cells were examined using myograph system and patch-clamp. Aging decreased the isoproterenol/forskolin-induced relaxation in the MCA. Large-conductance Ca2+-activated-K+ (BKCa) channel inhibitor, iberiotoxin, significantly attenuated the forskolininduced vasodilatation and hyperpolarization in the young group, but not in the aged group. The amplitude and frequency of spontaneous transient outward currents (STOCs) were significantly decreased in the aged group. Single channel recording revealed that the mean open time of BKCa channels were decreased, while an increased mean closed time of BKCa channels were found in the aged group. The Ca2+/voltage sensitivity of the channels was decreased accompanied by reduced BKCa α and β1-subunit, the expression of RyR2, PKA-Cα and PKA-Cβ subunits were also declined in the aged group. Aging induced down-regulation of PKA/BKCa pathway in cerebral artery in rats. The results provides new information on further understanding in cerebrovascular diseases resulted from agerelated cerebral vascular dysfunction.

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Coverage:

811-823

Source:

Physiological research | 2022 Volume:71 | Number:6

Harvested from:

CDK

Metadata only:

false