LY294002 Inhibits Intermediate Conductance Calcium-Activated Potassium (KCa3.1) Current in Human Glioblastoma Cells

被引：4

作者：

Caglioti, Concetta ^{[1
,2
]}

Palazzetti, Federico ^{[1
]}

Monarca, Lorenzo ^{[1
,2
]}

Lobello, Raffaele ^{[3
]}

Ceccarini, Maria Rachele ^{[4
]}

Iannitti, Rossana Giulietta ^{[5
]}

Russo, Roberta ^{[1
]}

Ragonese, Francesco ^{[1
]}

Pennetta, Chiara ^{[1
]}

De Luca, Antonella ^{[1
]}

Codini, Michela ^{[4
]}

Fioretti, Bernard ^{[1
]}

机构：

[1] Univ Perugia, Dept Chem Biol & Biotechnol, Perugia, Italy

[2] Univ Perugia, Perugia Med Sch, Dept Med, Perugia, Italy

[3] Relab Srl, Genoa, Italy

[4] Univ Perugia, Dept Pharmaceut Sci, Perugia, Italy

[5] S&R Farmaceutici SpA Bastia Umbra, Perugia, Italy

来源：

FRONTIERS IN PHYSIOLOGY | 2022年 / 12卷

关键词：

LY294002 (PI3K inhibitor); KCa3; 1 (intermediate-conductance Ca2+-activated K plus channel); glioblastoma; histamine (H1) receptor; calcium homeostasis; chemio and radioresistance; CA2+-ACTIVATED K+ CHANNEL; ION CHANNELS; HISTAMINE; 3-KINASE; MIGRATION;

D O I：

10.3389/fphys.2021.790922

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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 II beta (PI3KC2 beta). This modulation was observed also during the endogenous activation of KCa3.1 current with histamine. The principal action of PI3KC2 beta 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 PI3KC2 beta was proposed. Based on the roles of KCa3.1 and PI3KC2 beta in GB biology, a therapeutic implication was suggested to prevent chemo- and radioresistance mechanisms.

引用

页数：9

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