A role for receptor-operated Ca2+ entry in human pulmonary artery smooth muscle cells in response to hypoxia

Title:

A role for receptor-operated Ca2+ entry in human pulmonary artery smooth muscle cells in response to hypoxia

Creator:

Tang, C., To, W. K., Meng, F., Wang, Y., and Gu, Y.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:c3ecda16-bc5f-433d-aafb-af7422481065
uuid:c3ecda16-bc5f-433d-aafb-af7422481065
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, hypoxie, hypoxia, Hypoxic pulmonary vasoconstriction (HPV), hPASMC, Transient receptor potential channel (TRPC), AMP-activated kinase (AMPK), 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

Hypoxic pulmonary vasoconstric tion (HPV) is an important homeostatic mechanism in which increases of [Ca2+] i are primary events. In this study, primary cultured, human pulmonary artery smooth muscle cells (hPASMC) were used to examine the role of TRPC channels in mediating [Ca2+] i elevations during hypoxia. Hypoxia (PO2 about 20 mm Hg) evoked a transient [Ca2+] i elevation that was reduced by removal of extracellular calcium. Nifedipine and verapamil, blockers of vo ltage-gated calcium channels (VGCCs), attenuated th e hypoxia-induced [Ca2+] i elevation by about 30 %, suggesting the presence of alternate Ca2+ entry pathways. Expression of TRPC1 an d TRPC6 in hPASMC were found by RT-PCR and confirmed by Western blot analysis. Antagonists for TRPC, 2APB and SKF96365, significantly reduced hypoxia-induced [Ca2+] i elevation by almost 60 %. Both TRPC6 and TRPC1 were knocked down by siRNA, the loss of TRPC6 decreased hypoxic response down to 21 % of control, whereas the knockdown of TRPC1 reduced the hypoxia respon se to 85 %, suggesting that TRPC6 might play a central role in mediating hypoxia response in hPASMC. However, blockade of PLC pathway caused only small inhibition of the hypoxia response. In contrast, AICAR, the agonist of AMP-activated kinase (AMPK), induced a gradual [Ca2+] i elevation, whereas compound C, an antagonist of AMPK, almost abolished the hypoxia response. Ho wever, co-immunoprecipitation revealed that AMPK α was not colocalized with TRPC6. Our data supports a role for TRPC6 in mediation of the [Ca2+] i elevation in response to hypoxia in hPASMC and suggests that this response may be linked to cellular energy status via an activation of AMPK., C. Tang, W. K To, F. Meng, Y. Wang, Y. Gu., and Obsahuje bibliografii

Language:

English

Rights:

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

Source:

Physiological research | 2010 Volume:59 | Number:6

Harvested from:

CDK

Metadata only:

false