tailieunhanh - Báo cáo khoa học: The potassium channel subunit Kvb3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials

Pannexin 1 (Panx1), a member of the second gap junction protein family identified in vertebrates, appears to preferentially form non-junctional membrane channels. A candidate regulatory protein of Panx1 is the potas-sium channel subunit Kvb3, previously identified by bacterial two-hybrid strategies. | The potassium channel subunit Kvp3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials Stefanie Bunse1 Silviu Locovei2 Matthias Schmidt1 Feng Qiu2 Georg Zoidl1 3 Gerhard Dahl2 and Rolf Dermietzel1 1 Department of Neuroanatomy Molecular Brain Research Ruhr University Bochum Germany 2 Department of Physiology Biophysics University of Miami Schoolof Medicine Miami FL USA 3 Department of Cytology Ruhr University Bochum Germany Keywords channel interacting proteins potassium channel subunit drug sensitivity modulation Correspondence R. Dermietzel Department of Neuroanatomy and Molecular Brain Research Ruhr University Bochum UniversitatsstraBe 150 MA 6 159 44780 Bochum Germany Fax 49 234 321 4655 Tel 49 234 322 5003 E-mail Received 24 June 2009 revised 21 August 2009 accepted 27 August 2009 doi Pannexin 1 Panxl a member of the second gap junction protein family identified in vertebrates appears to preferentially form non-junctional membrane channels. A candidate regulatory protein of Panx1 is the potassium channel subunit Kvb3 previously identified by bacterial two-hybrid strategies. Here we report on the physical association of Panx1 with Kvb3 by immunoprecipitation when co-expressed in a neuroblastoma cell line Neuro2A . Furthermore in vivo co-expression of Panx1 and Kvb3 was shown to occur in murine hippocampus and cerebellum. Kvb3 is known to accelerate inactivation of otherwise slowly inactivating potassium channels under reducing conditions. We subsequently found that Panx1 channel currents exhibit a significant reduction when exposed to reducing agents and that this effect is attenuated in the presence of Kvb3. Apparently Kvb3 is involved in regulating the susceptibility of Panx1 channels to redox potential. Furthermore the Panx1 channel blockers carbenoxolone and Probenecid were less effective in inhibiting Panx1 currents when Kvb3 was co-expressed. The influence of Kvb3 .