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Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth

Authors :
Florian Gackière
Marine Warnier
Maria Katsogiannou
Sandra Derouiche
Philippe Delcourt
Etienne Dewailly
Christian Slomianny
Sandrine Humez
Natalia Prevarskaya
Morad Roudbaraki
Pascal Mariot
Source :
Biology Open, Vol 2, Iss 9, Pp 941-951 (2013)
Publication Year :
2013
Publisher :
The Company of Biologists, 2013.

Abstract

Summary 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.

Details

Language :
English
ISSN :
20466390
Volume :
2
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Biology Open
Publication Type :
Academic Journal
Accession number :
edsdoj.f0f4bb40b84642f7bdaf48027e73e43f
Document Type :
article
Full Text :
https://doi.org/10.1242/bio.20135215