Inhibitory effect of the DA uptake blocker GBR 12909 on sodium channels of hippocampal neurons.
The effect of the selective dopamine uptake inhibitor GBR 12909 on TTX-sensitive sodium channels of cultured hippocampal neurons was investigated using whole cell patch-clamp technique. GBR 12909 dose-dependently inhibited sodium currents evoked by trains of depolarizing pulses with an IC50 of 6.3 microM. A weaker inhibition (IC50 = 17-35 microM) could be observed when currents were evoked by either single pulse depolarization or from hyperpolarized holding membrane potential. These data indicate that the extent of inhibition caused by GBR 12909 depends on the physiological activity pattern of neurons. Our results suggest that caution is needed for the interpretation of data when GBR 12909 is used for the inhibition of dopamine uptake at concentrations above the submicromolar range.
Mike
Arpad
A
Department of Pharmacology, Hungarian Academy of Sciences, Budapest, Hungary.
Karoly
Robert
R
Vizi
E Sylvester
ES
Kiss
Janos P
JP
D000818:Animals; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects*
D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015222:Sodium Channels; C043425:vanoxerine