Phencyclidine in low doses selectively blocks a presynaptic voltage-regulated potassium channel in rat brain.
Phencylidine (PCP) is a major drug of abuse in the United States. It produces a toxic confusional psychosis in man. We show here that nanomolar to micromolar concentrations of PCP and behaviorally active congeners selectively block voltage-regulated noninactivating (or very slowly inactivating) presynaptic K channels in the brain. The rank order of potency for blockage of these K channels parallels both the relative ability of these agents to produce characteristic behavioral deficits in rats and their ability to displace [3H]PCP from its high-affinity binding sites in brain. In view of the enhanced voltage-gated Ca influx that would be expected to accompany blockage of presynaptic K channels, this mechanism could explain the excessive neurotransmitter release that is characteristic of PCP intoxication.
D K
DK
Bartschat
M P
MP
Blaustein
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D010622:Phencyclidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D011868:Radioisotopes; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D007473:Ion Channels; D011868:Radioisotopes; C012058:tenocyclidine; D010622:Phencyclidine; D012413:Rubidium; D011188:Potassium; D002118:Calcium