Figure 2: Ghrelin increases spontaneous firing of dopaminergic neurons via the GHS-R1a-PLC-PKC pathway.
From: Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels
(a) Raw traces show the spontaneous firing in the absence or presence of ghrelin and GHS-R1a antagonist D-[Lys3]-GHRP-6. Ghrelin (10 nM) increased firing frequency and D-[Lys3]-GHRP-6 (50 μM) alone had no effect on neuronal firing. Co-application of D-[Lys3]-GHRP-6 and ghrelin abolished stimulatory effect of ghrelin on neuronal firing. (b) A summary of statistical analysis for firing frequency from a (n=7). Each bar represents the mean±s.e.m. **P<0.01, Ghrelin versus Control; **P<0.01, Ghrelin versus D-[Lys3]-GHRP-6; **P<0.01, Ghrelin versus (D-[Lys3]-GHRP-6 + Ghrelin); F=4.950, analysis of variance (ANOVA) followed by Student-Newman-Keuls (S-N-K) test. (c–f) Summary of effects of inhibitors on ghrelin signalling transduction pathways. Both PLC inhibitor U-73122 and PKC inhibitor GF109203X diminished ghrelin effect. (c) PLC inhibitor U-73122 (10 μM) alone had no effect on neuronal firing, co-application of U-73122 (10 μM) and ghrelin (10 nM) abolished stimulatory effect of ghrelin on neuronal firing. (d) A summary of statistical analysis for firing frequency from c (n=7). Each bar represents the mean±s.e.m. *P<0.05, Ghrelin versus Control; *P<0.05, Ghrelin versus U-73122; *P<0.05, Ghrelin versus (U-73122 + Ghrelin); F=3.9, ANOVA followed by S-N-K test. (e) PKC inhibitor GF109203X (5 μM) alone had no effect on neuronal firing, co-application of GF109203X (5 μM) and ghrelin (10 nM) abolished stimulatory effect of ghrelin on neuronal firing. (f) A summary of statistical analysis for firing frequency from e (n=9). Each bar represents the mean±s.e.m. *P<0.05, Ghrelin versus Control; **P<0.01, Ghrelin versus GF109203X; **P<0.01, Ghrelin versus (GF109203X + Ghrelin); F=5.807, ANOVA followed by S-N-K test.
