Modulation of the respiratory rhythm by gap-junction blockers 18-α-glycyrrhetinic acid and 18-β-glycyrrhetinic acid

Gap junction proteins are expressed in the pre-Bötzinger complex of the respiratory network but it remains under discussion how they modulate the respiratory rhythm generation. In the present study we tested whether the gap junction blockers 18-β-glycyrrhetinic acid (18-βGA) and 18-α-glycyrrhetinic acid (18-α-GA) change either the phrenic nerve (PN) discharge frequency or amplitude. The PN discharge was recorded using the working heart-brainstem preparation of adult wistar rats (P22P28) exposed to increasing concentrations of the gap junction blockers (0.1; 1; 10; 20 μM). With the two lower concentrations (0.1; 1 μM) of 18-β-GA, PN discharge frequency decreased to 46±15% (p=0.007) of the control value while it increased to 173±57% (p=0.16) with the two higher concentrations (10; 20 μM). Surprisingly, with 18-α-GA the PN discharge frequency was not significantly changed with any of the concentrations used. Enhancing the respiratory drive with 12% CO2, the PN discharge frequency increased tendencially with rising concentrations of 18-β-GA, but again no significant change was observed with 18-α-GA. PN-amplitudes were slightly reduced over the course of the experiments, while the frequency of the heartbeat was not significantly changed at any time with any concentration.