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. Author manuscript; available in PMC: 2007 Nov 6.
Published in final edited form as: Brain Res. 2006 Sep 20;1118(1):66–74. doi: 10.1016/j.brainres.2006.08.033

Figure 4.

Figure 4

The tonic current is not blocked by the competitive GABA antagonist gabazine. A. The response of a typical glutamatergic neuron to 10 μM bicuculline is illustrated in the initial part of the trace. In contrast, 30 μM gabazine has no effect on the tonic current in the same neuron while the combination of bicuculline and gabazine again blocks the tonic current. Note that while gabazine is ineffective alone, it does partially occlude the ability of bicuculline to block the tonic current as switching from the combination of gabazine and bicuculline to bicuculline alone results in an additional amount of block (average 37.3 ± 11.0%; n = 7). B. The same experiment was repeated in a GABAergic neuron. At the −20 mV holding potential, there is continual release of GABA as seen by the larger noise amplitude in the baseline current and the more pronounced block of that noise by the GABA antagonists. In this case both gabazine and bicuculline block the tonic current. Note the additional block that occurs with the addition of bicuculline to gabazine (average 30.1 ± 11.3%; n = 4). This portion of the current that is not blocked by gabazine represents the spontaneous tonic current in inhibitory neurons. C. One possible explanation for the lack of direct gabazine effect is that the tonic current is mediated by neurosteroids (see text for details). While gabazine is a poor antagonist of steroid mediated currents, it strongly interferes with bicuculline block of steroid gated currents. Gabazine partially blocked the current mediated by 0.3 μM 3α5αP and strongly occluded bicuculline block as illustrated by the increase in bicuculline block when gabazine was removed (n = 4). Note that gabazine was much more effective in occluding bicuculline block of steroid mediated currents (average 3.5 ± 1.3% additional block from the combination of gabazine and bicuculline) compared to the tonic current (average 76.6 ± 5.5% additional block from the combination). In all panels, holding potential is −20 mV with a cesium methanesulfonate pipette solution.