Carbenoxolone induced depression of rhythmogenesis in the pre-B？tzinger Complex

Whereas neither of the control treatments [artificial cerebrospinal fluid (aCSF) or GZA (50 μM)] noticeably affected preB？tC rhythmogenesis, CBX (50 μM) decreased the frequency, area and amplitude of population bursts, eventually terminating population burst production after 45–60 min. Both CBX and GZA decreased neuronal Rin and induced an outward holding current. Although neither agent altered the steady state component of IK evoked by depolarizing voltage steps, CBX, but not GZA, increased peak INa.The data presented herein are consistent with the notion that gap junction communication is important for preB？tC rhythmogenesis. By comparing the effects of CBX and GZA on membrane properties our data a) demonstrate that depression of preB？tC rhythmogenesis by CBX results from actions on another variable or other variables; and b) show that this comparative approach can be used to evaluate the potential contribution of other non-specific actions (e.g., Ca++ conductances or active transport) of CBX, or other uncouplers, in their alteration of preB？tC rhythmogenesis, or the functioning of other networks.Located within the ventrolateral medulla the preB？tC is a central pattern generating neuronal network that rhythmically produces bursts of action potentials that are important for respiratory rhythmogenesis [1-3]. Regarding inter-cellular communication, most research on respiratory rhythmogenesis has focused on chemical synaptic transmission and neuromodulation [4-11]. Recent research has begun examining the potential contribution of electrical and cytoplasmic coupling via gap junctions in the functioning of central respiratory networks [12-19]. Mammalian gap junctions, like ion channels, are multi-unit structures of integral membrane proteins [20,21]. The best studied of these proteins are connexins (Cx), although pannexins are also expressed in mammals [22,23]. A connexin-based gap junction channel is composed of two hemi-channels, or connexons, that together span the m