Suppression of kainate-evoked AMPA receptor mediated responses by lanthanum in rat sacral dorsal commissural neurons.
The effect of lanthanum (La) on kainate (KA) responses in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) was investigated using the nystatin-perforated patch-recording configuration under voltage-clamp conditions. The responses to KA were mediated by activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in SDCN neurons. La(3+) reversibly inhibited KA (100 microM) activated currents (I(KA)) in a concentration-dependent manner over the range from 30 microM to 30 mM, with IC(50) values of 0.64 +/- 0.06 mM at a holding potential (V(H)) of -40 mV. Our further study indicated that the effects of La(3+) on I(KA) were voltage independent. Moreover, the inhibition was not use dependent and was not overcome by increasing the concentration of agonist. These findings indicate that La(3+) is an efficacious inhibitor of AMPA receptor mediated responses which may contribute to its cytotoxic effect.
Department of Anatomy and K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
Zhen
Z
Hong
Dian-Shi
DS
Wang
Shun-Yan
SY
Lu
Ji-Shuo
JS
Li
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D007811:Lanthanum / Q000494:pharmacology*; D008160:Lumbosacral Plexus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D007811:Lanthanum; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007608:Kainic Acid