GABAergic influences on bullfrog breathing rhythmogenesis and central CO 2 chemosensitivity

An increase in ventilatory frequency in response to elevated CO 2 levels (hypercapnia) may be mediated in part by the inhibition of central γ‐aminobutyric acid (GABA) signaling. GABA acts both on a fast synaptic chloride channel receptor (GABA A R) and a G‐protein coupled metabotropic receptor (GABA B R). We evaluated the effects of bath application of GABA and selective agonists of GABA A and GABA B receptors on control of breathing and central responses to hypercapnia in the isolated bullfrog brainstem preparation. GABA A R agonists muscimol and isoguvacine eliminated gill/buccal‐related neural activity and reduced lung burst frequency and amplitude. These responses were reversed with the addition of GABA A R antagonists bicuculline and GABAzine. Baclofen, a GABA B R agonist caused a reduction in lung burst activity; however, gill/buccal burst activity was not significantly affected. Preliminary results suggest that responses to hypercapnia are only affected by GABA A R pathways and only when the agonist concentration is high (1.0 μM muscimol). GABA A R mediated reductions in lung activity occurred at all metamorphic stages tested, the percent change in lung activity increased with development, suggesting a developmental increase in GABA A R occurs concurrent with developmental reductions in ventilatory‐related GABA B R. These data do not support the direct role of GABA in central hypercapnic ventilatory responses but do provide insight into the role of GABA signaling in bullfrog breathing control. Supported by NIH U54NS041069‐06AI