title: Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth.
abstract: It is strongly suspected that potassium (K(+)) channels are involved in various aspects of prostate cancer development, such as cell growth. However, the molecular nature of those K(+) channels implicated in prostate cancer cell proliferation and the mechanisms through which they control proliferation are still unknown. This study uses pharmacological, biophysical and molecular approaches to show that the main voltage-dependent K(+) current in prostate cancer LNCaP cells is carried by large-conductance BK channels. Indeed, most of the voltage-dependent current was inhibited by inhibitors of BK channels (paxillin and iberiotoxin) and by siRNA targeting BK channels. In addition, we reveal that BK channels constitute the main K(+) channel family involved in setting the resting membrane potential in LNCaP cells at around -40 mV. This consequently promotes a constitutive calcium entry through T-type Cav3.2 calcium channels. We demonstrate, using single-channel recording, confocal imaging and co-immunoprecipitation approaches, that both channels form macromolecular complexes. Finally, using flow cytometry cell cycle measurements, cell survival assays and Ki67 immunofluorescent staining, we show that both BK and Cav3.2 channels participate in the proliferation of prostate cancer cells.
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Bâtiment SN3, Université Lille 1 , 59655 Villeneuve d'Ascq Cédex , France.
authors.forename: Florian
authors.initials: F
authors.lastname: Gackière
authors.forename: Marine
authors.initials: M
authors.lastname: Warnier
authors.forename: Maria
authors.initials: M
authors.lastname: Katsogiannou
authors.forename: Sandra
authors.initials: S
authors.lastname: Derouiche
authors.forename: Philippe
authors.initials: P
authors.lastname: Delcourt
authors.forename: Etienne
authors.initials: E
authors.lastname: Dewailly
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.forename: Sandrine
authors.initials: S
authors.lastname: Humez
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
authors.forename: Morad
authors.initials: M
authors.lastname: Roudbaraki
authors.forename: Pascal
authors.initials: P
authors.lastname: Mariot
keywords: BK channels; CACNA1H; Cancer cell growth; Cav3.2; KCa1.1; Proliferation; Prostate; T-type calcium channels