{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:43:36Z","timestamp":1790815416271,"version":"4.1.0"},"reference-count":33,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,3,1]]},"abstract":"<jats:p>We used patch clamp techniques to study the inhibitory effects of pentobarbital and barbital on nicotinic acetylcholine receptor channels from BC3H-1 cells. Single channel recording from outside-out patches reveals that both drugs cause acetylcholine-activated channel events to occur in bursts. The mean duration of gaps within bursts is 2 ms for 0.1 mM pentobarbital and 0.05 ms for 1 mM barbital. In addition, 1 mM barbital reduces the apparent single channel current by 15%. Both barbiturates decrease the duration of openings within a burst but have only a small effect on the burst duration. Macroscopic currents were activated by rapid perfusion of 300\u2002\u03bcM acetylcholine to outside-out patches. The concentration dependence of peak current inhibition was fit with a Hill function; for pentobarbital, Ki = 32 \u03bcM, n = 1.09; for barbital, Ki = 1900 \u03bcM, n = 1.24. Inhibition is voltage independent. The kinetics of inhibition by pentobarbital are at least 30 times faster than inhibition by barbital (3 ms vs. &amp;lt;0.1 ms at the Ki). Pentobarbital binds \u226510-fold more tightly to open channels than to closed channels; we could not determine whether the binding of barbital is state dependent. Experiments performed with both barbiturates reveal that they do not compete for a single binding site on the acetylcholine receptor channel protein, but the binding of one barbiturate destabilizes the binding of the other. These results support a kinetic model in which barbiturates bind to both open and closed states of the AChR and block the flow of ions through the channel. An additional, lower-affinity binding site for pentobarbital may explain the effects seen at &amp;gt;100 \u03bcM pentobarbital.<\/jats:p>","DOI":"10.1085\/jgp.109.3.401","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:50:20Z","timestamp":1027702220000},"page":"401-414","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Mechanisms of Barbiturate Inhibition of Acetylcholine Receptor Channels"],"prefix":"10.1085","volume":"109","author":[{"given":"James P.","family":"Dilger","sequence":"first","affiliation":[{"name":"From the *Department of Anesthesiology, \u2021Department of Physiology and Biophysics, University at Stony Brook, Stony Brook, New York 11794-8480; and \u2016\u2016Klinik f\u00fcr An\u00e4sthesiologie, Universit\u00e4t Bonn, Bonn 53105, Germany"},{"name":"From the *Department of Anesthesiology, \u2021Department of Physiology and Biophysics, University at Stony Brook, Stony Brook, New York 11794-8480; and \u2016\u2016Klinik f\u00fcr An\u00e4sthesiologie, Universit\u00e4t Bonn, Bonn 53105, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Boguslavsky","sequence":"additional","affiliation":[{"name":"From the *Department of Anesthesiology, \u2021Department of Physiology and Biophysics, University at Stony Brook, Stony Brook, New York 11794-8480; and \u2016\u2016Klinik f\u00fcr An\u00e4sthesiologie, Universit\u00e4t Bonn, Bonn 53105, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Barann","sequence":"additional","affiliation":[{"name":"From the *Department of Anesthesiology, \u2021Department of Physiology and Biophysics, University at Stony Brook, Stony Brook, New York 11794-8480; and \u2016\u2016Klinik f\u00fcr An\u00e4sthesiologie, Universit\u00e4t Bonn, Bonn 53105, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamir","family":"Katz","sequence":"additional","affiliation":[{"name":"From the *Department of Anesthesiology, \u2021Department of Physiology and Biophysics, University at Stony Brook, Stony Brook, New York 11794-8480; 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