Metabotropic glutamate receptors activate dendritic calcium waves and TRPM channels which drive rhythmic respiratory patterns in mice.

摘要: Respiration in vertebrates is generated by a compact network which located the lower brainstem but cellular mechanisms underlie persistent oscillatory activity of respiratory are yet unknown. Using two-photon imaging and patch-clamp recordings functional preparations mice containing pre-Botzinger complex (preBotC), we examined actions metabotropic glutamate receptors (mGluR1/5) on patterns. The agonist DHPG potentiated antagonist LY367385 depressed respiration-related activities. In inspiratory neurons, observed rhythmic activation non-selective channels had conductance 24 pS. Their was enhanced with membrane depolarization after elevation calcium from cytoplasmic side membrane. They were activated non-hydrolysable PIP2 analogue blocked flufenamate, ATP4− Gd3+. All these properties correspond well to those TRPM4 channels. Calcium slices revealed transients small clusters neurons present network. soma preceded waves dendrites dependent mGluR activation. Initiation propagation required influx release internal stores. TPRM4-like promoted generation bursts. Simulations communicated via dendritic showed emerging within neuronal its synchronization between clusters. experimental theoretical data provide subcellular basis for recently proposed group-pacemaker hypothesis describe novel mechanism rhythm networks.