Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by riluzole.
The action of riluzole, a neuroprotective drug, on cloned delayed rectifier K+ channels (Kv1.5 and Kv3.1) was examined using the whole-cell patch-clamp technique. Riluzole reversibly inhibited Kv1.5 currents in a concentration-dependent manner with an IC50 of 39.69+/-2.37 microM. G-protein inhibitors (pertussis toxin and GDPbetaS) did not prevent this inhibition of riluzole on Kv1.5. No voltage-dependent inhibition by riluzole was found over the voltage range in which channels are fully activated. Riluzole shifted the steady-state inactivation curves of Kv1.5 in a hyperpolarizing direction in a concentration-dependent manner. It accelerated the deactivation kinetics of Kv1.5 in a concentration dependent-manner, but had no effect on the steady-state activation curve. Riluzole exhibited a use-independent inhibition of Kv1.5. The effects of riluzole on Kv3.1, the Shaw-type K+ channel were also examined. Riluzole caused a concentration-dependent inhibition of Kv3.1 currents with an IC50 of 120.98+/-9.74 microM and also shifted the steady-state inactivation curve of Kv3.1 in the hyperpolarizing direction. Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents in a concentration-dependent manner and interacts directly with Kv1.5 by preferentially binding to the inactivated and to the closed states of the channel.
Ahn
H S
HS
Department of Physiology, Medical Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
Choi
J-S
JS
Choi
B H
BH
Kim
M-J
MJ
Rhie
D-J
DJ
Yoon
S-H
SH
Jo
Y-H
YH
Kim
M-S
MS
Sung
K-W
KW
Hahn
S J
SJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects*; D009479:Neuropeptides / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques / Q000379:methods; D037342:Pertussis Toxin / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D019782:Riluzole / Q000494:pharmacology*; D051670:Shaw Potassium Channels; D013873:Thionucleotides / Q000494:pharmacology
D051666:Kv1.5 Potassium Channel; D009479:Neuropeptides; D018696:Neuroprotective Agents; D024642:Potassium Channels, Voltage-Gated; D051670:Shaw Potassium Channels; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D019782:Riluzole; D037342:Pertussis Toxin