The augmentation of BK channel activity by nitric oxide signaling in rat cerebral arteries involves co-localized regulatory elements.

ABSTRACT: Large conductance, Ca²⁺-activated K⁺ (BK) channels control cerebrovascular tone; however, the regulatory processes influencing these channels remain poorly understood. Here, we investigate the cellular mechanisms underlying the enhancement of BK current in rat cerebral arteries by nitric oxide (NO) signaling. In isolated cerebral myocytes, BK current magnitude was reversibly increased by sodium nitroprusside (SNP, 100??M) and sensitive to the BK channel inhibitor, penitrem-A (100?nM). Fostriecin (30?nM), a protein phosphatase type 2A (PP2A) inhibitor, significantly prolonged the SNP-induced augmentation of BK current and a similar effect was produced by sildenafil (30?nM), a phosphodiesterase 5 (PDE5) inhibitor. Using proximity ligation assay (PLA)-based co-immunostaining, BK channels were observed to co-localize with PP2A, PDE5, and cGMP-dependent protein kinase (cGKI) (spatial restriction?

SUBMITTER: Kyle BD 

PROVIDER: S-EPMC5718322 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature