{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T13:32:51Z","timestamp":1747747971679},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1992,10,1]],"date-time":"1992-10-01T00:00:00Z","timestamp":717897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[1992,10]]},"abstract":"<jats:p>1. Phencyclidine (PCP) block of Ca2+ channel current in enzymatically dissociated neurones from the CA1 region of the adult guinea\u2010pig hippocampus was studied using whole\u2010cell voltage clamp techniques. Ca2+ channel current was recorded with 3 mM\u2010Ba2+ as the charge carrier. Na+ currents were blocked with tetrodotoxin and K+ currents were eliminated by using tetraethylammonium and N\u2010methyl\u2010D\u2010glucamine as the predominant extracellular and intracellular cations, respectively. 2. Peak Ca2+ channel current evoked by depolarization from \u201080 to \u201010 mV was reduced in a use\u2010dependent fashion by PCP. The apparent forward and reverse rate constants for block at the depolarized voltage were 10(6) s\u20101 M\u20101 and 11\u201014 s\u20101, respectively. These values were at least 60 times faster than the corresponding rates at the resting voltage. The steady\u2010state block produced by PCP increased in a concentration\u2010dependent fashion with an IC50 of 7 microM. Other dissociative anaesthetic drugs were substantially weaker inhibitors of the current (tiletamine &gt; dizocilpine (MK\u2010801) &gt; ketamine). 3. The Ca2+ channel current recorded under identical conditions in rat dorsal root ganglion neurones was less sensitive to blockade by PCP (IC50, 90 microM). 4. PCP block of the hippocampal Ca2+ channel current occurred in a voltage\u2010dependent fashion with the fractional block decreasing at positive membrane potentials. Analysis indicated that the PCP blocking site senses 56% of the transmembrane electric field. 5. Analysis of tail currents recorded at \u201080 mV demonstrated that PCP does not affect the voltage\u2010dependent or time\u2010dependent activation or deactivation of the Ca2+ channel current. 6. The rate and extent of inactivation of the Ca2+ channel current was maximal at \u201010 mV and diminished at more positive potentials. Experiments with Ba(2+)\u2010free external solution demonstrated that inactivation of the Ca2+ channels is largely voltage\u2010dependent and is not affected by Ba2+ influx. 7. PCP markedly increased the apparent extent of inactivation of the Ca2+ channel current during prolonged voltage steps. This increase in apparent inactivation was more pronounced at depolarized potentials. Inactivation at \u201010 mV proceeded in two exponential phases; PCP had little effect on the fast decay phase and caused a moderate speeding of the slow decay phase. Although block of the activated state evolved on the same time scale as inactivation, the apparent rate of inactivation was not increased in a concentration\u2010dependent fashion by PCP indicating that the block does not occur by a conventional open channel mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)<\/jats:p>","DOI":"10.1113\/jphysiol.1992.sp019328","type":"journal-article","created":{"date-parts":[[2014,12,17]],"date-time":"2014-12-17T15:27:34Z","timestamp":1418830054000},"page":"85-105","source":"Crossref","is-referenced-by-count":19,"title":["Phencyclidine block of calcium current in isolated guinea\u2010pig hippocampal neurones."],"prefix":"10.1113","volume":"456","author":[{"given":"J M","family":"Ffrench\u2010Mullen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M A","family":"Rogawski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1992,10]]},"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.1992.sp019328","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.1992.sp019328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T13:20:42Z","timestamp":1698153642000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.1992.sp019328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,10]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1992,10]]}},"alternative-id":["10.1113\/jphysiol.1992.sp019328"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.1992.sp019328","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,10]]}}}