Carbenoxolone induced depression of rhythmogenesis in the pre-Bötzinger Complex

Background Carbenoxolone (CBX), a gap junction uncoupler, alters the functioning of the pre-Botzinger Complex (preBotC), a central pattern generating neuronal network important for the production of respiratory rhythm in mammals. Even when isolated in a 1/2 mm-thick slice of medulla oblongata from neonatal mouse the preBotC continues producing periodic bursts of action potentials, termed population bursts that are thought to be important in generating various patterns of inspiration, in vivo. Whether gap junction communication contributes to preBotC rhythmogenesis remains unresolved, largely because existing gap junction uncouplers exert numerous non-specific effects (e.g., inhibition of active transport, alteration of membrane conductances). Here, we determined whether CBX alters preBotC rhythmogenesis by altering membrane properties including input resistance (Rin), voltage-gated Na+ current (INa), and/or voltage-gated K+ current (IK), rather than by blocking gap junction communication. To do so we used a medullary slice preparation, network-level recordings, whole-cell voltage clamp, and glycyrrhizic acid (GZA; a substance used as a control for CBX, since it is similar in structure and does not block gap junctions).