Lead-induced blockage of kainate-sensitive receptor channels.
The effects of bivalent lead on ion channels activated by kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) were studied using Xenopus oocytes microinjected with mRNA from rat brain. Lead reduced kainate-induced membrane currents in a reversible and dose-dependent manner, without affecting membrane currents induced by AMPA. Lead decreased the kainate currents with a concentration of 0.1 micromol/1 to 0.93 +/- 0.01 and with a concentration of 100 micromol/1 to 0.41 +/- 0.04 of the control values. The blocking effect of lead on kainate responses was voltage dependent. The inhibition was strongest at -90 mV to -70 mV and became weaker at more positive membrane potentials. The effect of lead on the kainate-induced membrane currents remained unchanged when the concentration of kainate was increased. Hence lead probably represents a noncompetitive channel-blocking agent for non-N-methyl-D-aspartate (NMDA) receptor channels activated by kainate.
Musshoff
U
U
Institut fur Physiologie, Münster, Germany.
Madeja
M
M
Binding
N
N
Witting
U
U
Speckmann
E J
EJ
D000818:Animals; D007473:Ion Channels / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology*; D007854:Lead / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D007473:Ion Channels; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid