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. 2013 Aug 27;591(Pt 22):5765–5790. doi: 10.1113/jphysiol.2013.253757

Figure 8. GABAB/sAHP antagonists decrease stimulus-induced long-lasting hyperpolarization in epileptic slices.

Figure 8

LFS (1 Hz) was applied to the VHC of bilateral hippocampi–VHC slices while recording intracellularly from bilateral CA3/CA1 pyramidal cells as shown in Fig. 7A in either (1) 4-AP (n= 4); (2) CGP-55845-HCl (1 μm) in 4-AP (n= 3); (3) UCL-2077 (10 μm) in 4-AP (n= 3); or (4) both CGP-55845-HCl + UCL-2077 in 4-AP (n= 3). A–D, a single trace showing evoked as well as non-evoked activity that occurs in the inter-stimulus interval (ISI) during 1 Hz electrical stimulation in each solution is shown in the left column. Traces are 1 s with stimulation marked by dots. Activity in the ISI is averaged across slices for each solution. The average (continuous line) ± SD (dotted line) is shown in the right column with the sample mean resting potential in grey. E, peak hyperpolarization amplitudes in each solution are measured as the lowest voltage of the averaged signal in the ISI after 100 ms per slice minus the resting potential of that cell. The mean hyperpolarization amplitudes across slices per solution are: (1) 7.1 ± 0.3 mV; (2) 4.6 ± 0.3 mV; (3) 4.7 ± 0.7 mV; and (4) 2.9 ± 0.7 mV for (1) 4-AP (n= 4); (2) CGP-55845-HCl in 4-AP (n= 3); (3) UCL-2077 in 4-AP (n= 3); and (4) both CGP-55845-HCl + UCL-2077 in 4-AP (n= 3), respectively. Hyperpolarization amplitude differs across groups (P < 0.0001, ANOVA, LSD (Tukey-Kramer) at P < 0.01 = 0.79 mV). F, hyperpolarization area is measured per solution as the sum of the averaged voltage potentials lower than the resting potential in the ISI minus the resting potential of that cell. The mean hyperpolarization areas across slices per solution are: (1) 63.8 ± 1.7 mV s; (2) 37.3 ± 8.7 mV s; (3) 12.1 ± 11.0 mV s; and (4) 11.3 ± 8.7 mV s for (1) 4-AP; (2) CGP-55845-HCl in 4-AP; (3) UCL-2077 in 4-AP; and (4) CGP-55845-HCl + UCL-2077 in 4-AP, respectively. There are significant differences in hyperpolarization area between groups (P < 0.0001, ANOVA, LSD (Tukey-Kramer) at P < 0.01 = 9.35 mV s). Bar graphs represent data means ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.