Differential regulation of Γ-aminobutyric acid receptor channels by diazepam and phenobarbital
dc.contributor.author | Twyman, Roy E. | en_US |
dc.contributor.author | Rogers, Carl J. | en_US |
dc.contributor.author | Macdonald, Robert L. | en_US |
dc.date.accessioned | 2007-04-06T18:52:28Z | |
dc.date.available | 2007-04-06T18:52:28Z | |
dc.date.issued | 1989-03 | en_US |
dc.identifier.citation | Twyman, Roy E.; Rogers, Carl J.; Macdonald, Robert L. (1989)."Differential regulation of Γ-aminobutyric acid receptor channels by diazepam and phenobarbital." Annals of Neurology 25(3): 213-220. <http://hdl.handle.net/2027.42/50330> | en_US |
dc.identifier.issn | 0364-5134 | en_US |
dc.identifier.issn | 1531-8249 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/50330 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=2471436&dopt=citation | en_US |
dc.description.abstract | The anticonvulsant activity of diazepam and phenobarbital may be mediated in part by enhancement of inhibition involving Γ-aminobutyric acid (GABA). While both diazepam and phenobarbital increase GABA receptor chloride current, they may have different mechanisms of action, since they bind to different sites on the GABA receptor—chloride channel complex. We used the patch clamp technique to compare the effects of diazepam and phenobarbital on single GABA receptor currents. Outside-out patches were obtained from mouse spinal cord neurons grown in cell culture for 2 to 4 weeks. GABA (2 ΜM) evoked single channel currents that occurred as single brief openings or in bursts of multiple openings. Diazepam (20 nM) and phenobarbital (500 ΜM) both increased the GABA receptor current by increasing mean open time without altering channel opening frequency. However, the temporal grouping of openings into bursts suggested that the enhancement occurred via different mechanisms. Diazepam increased the frequency of bursting GABA receptor currents with minimal effect on the duration of bursts. Phenobarbital increased the duration of bursting GABA receptor currents without altering the frequency of bursts. These results suggest that diazepam binds to a site that may enhance single channel burst frequency by increasing the affinity of GABA binding, while phenobarbital may stabilize the bursting open state of the channel by binding to a different modulatory site at or near the chloride channel. | en_US |
dc.format.extent | 817407 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Neuroscience, Neurology, and Psychiatry | en_US |
dc.title | Differential regulation of Γ-aminobutyric acid receptor channels by diazepam and phenobarbital | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Psychiatry | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI ; Neuroscience Laboratory Building, 1103 East Huron Street, Ann Arbor, MI 48104-1687 | en_US |
dc.identifier.pmid | 2471436 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/50330/1/410250302_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/ana.410250302 | en_US |
dc.identifier.source | Annals of Neurology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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