Abstract：
:Whole-cell voltage-clamp techniques were used to study the comparative effects of delta-9-tetrahydrocannabinol (THC) and its principal metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC), on the voltage-gated sodium current in neuroblastoma cells. The parent compound markedly depressed the inward sodium current with minimal reduction of the outward current, demonstrating that the effects of the drug were related to the membrane potential. In addition, THC reduced the reversal potential, indicating that the drug modified the ion selectivity of the channel. 11-OH-THC similarly depressed inward sodium current; however, in marked contrast to the effects of the parent compound, the drug equally depressed the outward voltage-gated sodium current, indicating that its effects were not related to the membrane potential. Furthermore, 11-OH-THC differed from THC in that it did not alter the reversal potential. The results demonstrate that THC and its 11-OH metabolite both reduce inward sodium current, but their effects on the outward current and ion selectivity are distinctly different. The sum of the actions of these two cannabinoids on the voltage-gated sodium channel provides a plausible cellular basis for THC's depression of action potentials in vivo and for some of its central depressant effects.
journal_name
Brain Resjournal_title
Brain researchauthors
Turkanis SA,Karler R,Partlow LMdoi
10.1016/0006-8993(91)91239-wsubject
Has Abstractpub_date
1991-09-27 00:00:00pages
245-50issue
1-2eissn
0006-8993issn
1872-6240pii
0006-8993(91)91239-Wjournal_volume
560pub_type
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