LY294002 Inhibits Intermediate Conductance Calcium-Activated Potassium (KCa3.1) Current in Human Glioblastoma Cells.
KCa3.1 (intermediate-conductance Ca2+-activated K+ channel)
LY294002 (PI3K inhibitor)
calcium homeostasis
chemio and radioresistance
glioblastoma
histamine (H1) receptor
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2021
2021
Historique:
received:
07
10
2021
accepted:
30
11
2021
entrez:
24
1
2022
pubmed:
25
1
2022
medline:
25
1
2022
Statut:
epublish
Résumé
Glioblastomas (GBs) are among the most common tumors with high malignancy and invasiveness of the central nervous system. Several alterations in protein kinase and ion channel activity are involved to maintain the malignancy. Among them, phosphatidylinositol 3-kinase (PI3K) activity and intermediate conductance calcium-activated potassium (KCa3.1) current are involved in several aspects of GB biology. By using the electrophysiological approach and noise analysis, we observed that KCa3.1 channel activity is LY294002-sensitive and Wortmannin-resistant in accordance with the involvement of PI3K class IIβ (PI3KC2β). This modulation was observed also during the endogenous activation of KCa3.1 current with histamine. The principal action of PI3KC2β regulation was the reduction of open probability in intracellular free calcium saturating concentration. An explanation based on the "three-gate" model of the KCa3.1 channel by PI3KC2β was proposed. Based on the roles of KCa3.1 and PI3KC2β in GB biology, a therapeutic implication was suggested to prevent chemo- and radioresistance mechanisms.
Identifiants
pubmed: 35069252
doi: 10.3389/fphys.2021.790922
pmc: PMC8782274
doi:
Types de publication
Journal Article
Langues
eng
Pagination
790922Informations de copyright
Copyright © 2022 Caglioti, Palazzetti, Monarca, Lobello, Ceccarini, Iannitti, Russo, Ragonese, Pennetta, De Luca, Codini and Fioretti.
Déclaration de conflit d'intérêts
RL was employed by the company Relab S.r.l. RI was employed by the company S&R Farmaceutici S.p.A Bastia Umbra. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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