Blockade of U50488H on sodium currents in acutely isolated mice hippocampal CA3 pyramidal neurons.
The effect of opioid agonist U50488H on Na(+) currents was examined in freshly dissociated hippocampal neurons of mice using the whole-cell patch clamp technique. U50488H (1-100 microM) caused a concentration dependent reversible inhibition of the voltage-activated sodium currents. IC50 of 15.5 microM and Hill constant of 1.4 were calculated respectively. The inhibitory actions of U50488H on I(Na) were still observed in the presence of 30 microM naloxone. Moreover, under the action of U50488H, repetitive stimulation induced further inhibition which was frequency-dependent. The activation curve did not change before and after application of 10 microM U50488H. However, after exposure to 10 microM U50488H and repetitive depolarizing at 10 Hz, frequency-dependent inhibition occurred, and a mean shift of half-activation membrane potential by +20 mV could be induced. The inactivation curve was significantly changed toward negative membrane potential with 10 microM U50488H, and further negative shift was observed after repetitive depolarizing at 10 Hz. Our results indicate that U50488H could directly inhibit neuronal Na(+) currents without involvement in the activation of kappa-opioid receptors.
Zou
B
B
National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China.
Chen
Y
Y
Wu
C
C
Zhou
P
P
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D015222:Sodium Channels; D013779:Tetrodotoxin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D012964:Sodium