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| Content Provider | PubMed Central |
|---|---|
| Author | Rogers, C. J. Twyman, R. E. Macdonald, R. L. |
| Abstract | 1. The effects of the benzodiazepine receptor agonist, diazepam (DZ), and the inverse agonist, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), on gamma-aminobutyric acid (GABAA) receptor single channel currents were characterized. Outside-out patches were obtained from somata of cultured mouse spinal cord neurones and voltage clamped at -75 mV (ECl = 0 mV). 2. GABA (2 microM) alone or with DZ (20-1000 nM) or DMCM (20-100 nM) was applied to patches by pressure ejection from blunt micropipettes. DZ enhanced GABAA receptor currents with an inverted U-shaped concentration-response curve. Mean steady-state currents were increased by low concentrations of DZ (20-50 nM). At higher concentrations of DZ, the enhancement was diminished. Mean steady-state currents were decreased by DMCM at all concentrations. 3. GABAA receptor channels opened most frequently to a 27 pS main conductance level and less frequently to a 19 pS subconductance level. Neither DZ nor DMCM altered the proportion of time spent at either of the conductance levels. The kinetic properties of the main conductance level were studied. 4. Neither DZ nor DMCM altered the mean GABAA receptor channel open or burst durations. Sums of three exponential functions were required to fit best open and burst duration-frequency histograms for GABA alone or with DZ or DMCM. No significant changes in the three time constants or areas of the three exponential functions for open or burst duration histograms were produced by DZ or DMCM. 5. With increasing concentrations of DZ up to 50 nM, GABA evoked an increased frequency of channel openings and bursts. With higher DZ concentrations, the magnitudes of the increase in channel opening and burst frequencies were reduced. At all concentrations of DMCM, GABA evoked a decreased frequency of channel openings and bursts. 6. Closed duration-frequency histograms for GABA alone or with DZ or DMCM were best fitted by sums of at least six exponential functions. The three shortest closed duration time constants were unchanged by DZ or DMCM. The three longest closed duration time constants were altered by DZ and DMCM, consistent with alterations in opening frequency. 7. DZ increased and DMCM decreased steady-state GABAA receptor current by increasing or decreasing channel opening frequency without altering mean channel open duration. We propose that DZ and DMCM alter GABAA receptor current by acting reciprocally to increase or decrease only, respectively, the apparent agonist association rate at the first of two proposed GABA binding steps without altering channel gating.(ABSTRACT TRUNCATED AT 400 WORDS) |
| Starting Page | 69 |
| File Format | |
| ISSN | 14697793 |
| e-ISSN | 14697793 |
| Journal | The Journal of Physiology |
| Issue Number | 1 |
| Volume Number | 475 |
| Language | English |
| Publisher Date | 1994-02-15 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
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