Figure 6: IH/O-A is blocked by OX2R but not OX1R antagonists. | Scientific Reports

Figure 6: IH/O-A is blocked by OX2R but not OX1R antagonists.

From: Hypocretin/Orexin Peptides Excite Rat Neuroendocrine Dopamine Neurons through Orexin 2 Receptor-Mediated Activation of a Mixed Cation Current

Figure 6

(A) Current clamp recording of the response to H/O-A of a TIDA neuron in the continuous presence of TTX and the OX1R antagonist SB334867 (1 μM). Scale bar 20 Sec. (Ai) Sharing its y-axis with the raw trace in A, is the mean (solid line) membrane potential in control, H/O-A + SB334867 and wash. Raw data used to produce averages shown as dashed lines (n = 6; ***P < 0.001; ANOVA repeated measures with post-hoc Tukey test). (Aii) Blockade of the OX1R receptor with SB334867 failed to abolish H/O-A induced depolarisation, however, under these conditions the resultant depolarisation was significantly different to that of control (Control n = 11; H/O-A in SB334867 n = 6; ***P < 0.001; unpaired t-test). Box plot organised as Fig. 2Bii. (B) Current clamp recording of the response of a TIDA neuron to H/O-A in the presence of TTX and the selective OX2R Antagonist TCS OX2 29 (1 μM) (Scale bar 10 Sec). (Bi) Sharing its y-axis with the raw trace in B is the mean (solid line) membrane potential in control and H/O-A + TCS OX2 29. Raw data used to produce averages shown as dashed lines (n = 6; P > 0.05; paired t-test). (Bii) The presence of OX2R antagonist TCS OX2 29 completely abolished TIDA neurons response to H/O-A, an effect statistically different from the H/O-A induced depolarisation under control conditions (Control n = 11; TCS OX2 29 n = 9; ***P < 0.001; unpaired t-test). Box plot organised as Fig. 2Bii. (C) Current clamp recording of the response of a TIDA neuron in the continuous presence of TTX to selective OX2R agonist Ala-Leu-Orexin-B (500 nM) (Scale bar 10 Sec). (Ci) Sharing its y-axis with the raw trace in C, is the mean (solid line) membrane potential in control, Ala-Leu-Orexin-B and wash. Raw data used to produce averages shown as dashed lines (n = 6; ***P < 0.001; ANOVA repeated measures with post-hoc Tukey test). (Cii) Application of Ala-Leu-Orexin-B induced a depolarisation that was statistically indistinguishable from the H/O-A and H/O-B induced depolarisations under control conditions (Control n = 11; Leu-Ala-Orexin-B n = 9; H/O-B n = 3; P > 0.05; ANOVA with post-hoc Tukey test). Box plot organised as Fig. 2Bii.

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