@entity1245 and beta-carboline regulation of single XXXX receptor channels of @entity19 spinal neurones in culture.

@entity3175 @entity1246 @entity19 @entity25528 @entity1245 @entity8771
1. The effects of the @entity1245 receptor agonist, @entity3175 (DZ), and the inverse agonist, @entity25528 ( @entity25528 ), on @entity1246 ( @entity8771 ) receptor single channel currents were characterized. Outside-out patches were obtained from somata of cultured @entity19 spinal cord neurones and voltage clamped at -75 mV (ECl = 0 mV). 2. @entity1246 (2 microM) alone or with DZ (20-1000 nM) or @entity25528 (20-100 nM) was applied to patches by pressure ejection from blunt micropipettes. DZ enhanced @entity8771 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 @entity25528 at all concentrations. 3. @entity8771 receptor channels opened most frequently to a 27 pS main conductance level and less frequently to a 19 pS subconductance level. Neither DZ nor @entity25528 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 @entity25528 altered the mean @entity8771 receptor channel open or burst durations. Sums of three exponential functions were required to fit best open and burst duration-frequency histograms for @entity1246 alone or with DZ or @entity25528 . 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 @entity25528 . 5. With increasing concentrations of DZ up to 50 nM, @entity1246 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 @entity25528 , @entity1246 evoked a decreased frequency of channel openings and bursts. 6. Closed duration-frequency histograms for @entity1246 alone or with DZ or @entity25528 were best fitted by sums of at least six exponential functions. The three shortest closed duration time constants were unchanged by DZ or @entity25528 . The three longest closed duration time constants were altered by DZ and @entity25528 , consistent with alterations in opening frequency. 7. DZ increased and @entity25528 decreased steady-state @entity8771 receptor current by increasing or decreasing channel opening frequency without altering mean channel open duration. We propose that DZ and @entity25528 alter @entity8771 receptor current by acting reciprocally to increase or decrease only, respectively, the apparent agonist association rate at the first of two proposed @entity1246 binding steps without altering channel gating.(ABSTRACT TRUNCATED AT 400 WORDS)
