AUTHOR=Caglioti Concetta , Palazzetti Federico , Monarca Lorenzo , Lobello Raffaele , Ceccarini Maria Rachele , Iannitti Rossana Giulietta , Russo Roberta , Ragonese Francesco , Pennetta Chiara , De Luca Antonella , Codini Michela , Fioretti Bernard TITLE=LY294002 Inhibits Intermediate Conductance Calcium-Activated Potassium (KCa3.1) Current in Human Glioblastoma Cells JOURNAL=Frontiers in Physiology VOLUME=Volume 12 - 2021 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.790922 DOI=10.3389/fphys.2021.790922 ISSN=1664-042X ABSTRACT=

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.