{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:06:01Z","timestamp":1776755161722,"version":"3.51.2"},"reference-count":43,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1997,7,1]]},"abstract":"<jats:p>Twitchell, W., S. Brown, and K. Mackie. Cannabinoids inhibit N- and P\/Q-type calcium channels in cultured rat hippocampal neurons. J. Neurophysiol. 78: 43\u201350, 1997. Cannabinoids and their analogues have been found to inhibit N- and P\/Q-type Ca<jats:sup>2+<\/jats:sup>currents in cell lines and sympathetic neurons transfected with cannabinoid CB1 receptor. However, the effects of cannabinoids on Ca<jats:sup>2+<\/jats:sup>currents in the CNS are largely unexplored. In this study we investigated whether these compounds inhibit Ca<jats:sup>2+<\/jats:sup>channels in cultured rat hippocampal neurons. With the use of antibodies directed against the amino-terminus of the CB1 receptor, we found that in 5-day cultures pyramidally shaped neurons expressed somatic CB1 receptors, whereas in 4-wk cultures the receptor was predomintely located on neurites. In early cultures, the cannabimimetic WIN 55,212-2 reversibly inhibited whole cell Ba<jats:sup>2+<\/jats:sup>current in a concentration-dependent ( K<jats:sub>1\/2<\/jats:sub>= 21 nM) and pertussis-toxin-sensitive fashion. Inhibition was reduced by the CB1 antagonist SR141716. The current was unaffected by the nonpsychoactive enantiomer WIN 55,212-3. Maximal inhibition by the nonclassical cannabinoid agonist CP 55,940 and by an endogenous cannabinoid, anandamide, were similar to that seen with maximal concentrations of WIN 55,212-2. The Ba<jats:sup>2+<\/jats:sup>current modulated by cannabinoids was carried by N-type (\u03c9-conotoxin-GVIA-sensitive) and P\/Q-type (\u03c9-conotoxin-MVIIC-sensitive) channels. These results demonstrate cannabinoid-receptor-mediated inhibition of distinct Ca<jats:sup>2+<\/jats:sup>channels in central neurons. Because the channels that underlie these currents are chiefly located presynaptically, and are required for evoked neurotransmitter release, our results suggest a major role for cannabinoids (endogenous and exogenous) in the modulation of synaptic transmission at CNS synapses.<\/jats:p>","DOI":"10.1152\/jn.1997.78.1.43","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T05:44:01Z","timestamp":1514180641000},"page":"43-50","source":"Crossref","is-referenced-by-count":435,"title":["Cannabinoids Inhibit N- and P\/Q-Type Calcium Channels in Cultured Rat Hippocampal Neurons"],"prefix":"10.1152","volume":"78","author":[{"given":"W.","family":"Twitchell","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and"}]},{"given":"S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and"}]},{"given":"K.","family":"Mackie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and"},{"name":"Department of Physiology and Biophysics, School of Medicine, University of Washington, Seattle, Washington 98195"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/340153a0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.17.7834"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb08815.x"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1042\/bj3120637"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.75.5.2017"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14321.x"},{"key":"B7","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/S0022-3565(25)09495-9","volume":"273","author":"Deadwyler S. 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