Figure 3. Lack of Vglut3 disrupts respiratory control and thermogenesis in the cold.

Aa and b, examples of changes in central respiratory drive induced by acidosis in Control (a) and Vglut3^−/− pups (b) in vitro. Int C4: integrated C4 activity (C4). Ac, the effect of acidosis (shaded) on mean phrenic burst frequency (PBf) was significantly increased in Vglut3^−/− pups (n = 4) when compared to control pups (n = 12, P < 0.05; Student's unpaired t test). Ba and b, examples of changes in central respiratory drive induced by anoxia in control (a) and Vglut3^−/− pups (b) in vitro. Bc, the effect of anoxia (shaded) was significantly increased in Vglut3^−/− pups (n = 8) when compared to controls (n = 18, P < 0.001). C, examples of plethysmographic recordings in 6-day-old Vglut3^−/− and control pups during normoxia (a), hypoxia (10% O₂) (b) and post-hypoxia (Cc). Da–c, breathing variables: ventilation (), tidal volume (V_T) and breathing frequency (R_f). Vglut3^−/−pups (n = 63) displayed decreased ventilation during both normoxia and hypoxia, compared to control pups (n = 200). Both groups displayed a biphasic response to hypoxia (shaded), with the initial increase in being followed by a marked decrease (under the control of V_T and R_f). Ea–c, percentage change in breathing variables in response to hypoxia, relative to pre-hypoxic levels (hyperpnoeic response and hypoxic decline); HVD was significantly lower in Vglut3^−/− pups. Dd, oxygen consumption () at 26°C under normoxia and in response to hypoxia (shaded) in 6-day-old Vglut3^−/− (n = 7) and control pups (n = 29). The smaller in Vglut3^−/− pups (P < 0.001) reflected their impaired thermogenesis. Ed, percentage change in relative to pre-hypoxic levels was smaller in Vglut3^−/− pups. *P < 0.05; **P < 0.01; ***P < 0.001, Student's unpaired t test. Values shown are group means ± SEM. See Tables 1 and 2 for full statistical analyses.