Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells.
Heteromeric KCNQ5/Q3 channels were stably expressed in Chinese Hamster ovary cells and characterized using the whole cell voltage-clamp technique. KCNQ5/Q3 channels were activated by the novel anticonvulsant, retigabine (EC(50) 1.4 microM) by a mechanism that involved drug-induced, leftward shifts in the voltage-dependence of channel activation (-31.8 mV by 30 microM retigabine). KCNQ5/Q3 channels were inhibited by linopirdine (IC(50) 7.7 microM) and barium (IC(50) 0.46 mM), at concentrations similar to those required to inhibit native M-currents. These findings identify KCNQ5/Q3 channels as a molecular target for retigabine and raise the possibility that activation of KCNQ5/Q3 channels may be responsible for some of the anti-convulsant activity of this agent. Furthermore, the sensitivity of KCNQ5/Q3 channels to linopirdine supports the possibility that potassium channels comprised of KCNQ5 and KCNQ3 may make a contribution to native M-currents.
Wickenden
A D
AD
ICAgen Inc., 4222 Emperor Boulevard, Durham, North Carolina, NC 27703, USA. awickenden@icagen.com
Zou
A
A
Wagoner
P K
PK
Jegla
T
T
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D016466:CHO Cells; D002219:Carbamates / Q000494:pharmacology; D006224:Cricetinae; D004594:Electrophysiology; D007211:Indoles / Q000494:pharmacology; D051659:KCNQ3 Potassium Channel; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010655:Phenylenediamines / Q000494:pharmacology; D010957:Plasmids; D015221:Potassium Channels / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014982:Xenopus laevis
D000927:Anticonvulsants; D002219:Carbamates; D007211:Indoles; D051659:KCNQ3 Potassium Channel; D010655:Phenylenediamines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; C101866:ezogabine; D001464:Barium; C061017:linopirdine