Stable respiratory activity requires both P/Q-type and N-type voltage-gated calcium channels.

摘要: P/Q-type voltage-gated calcium channels (Ca(v)2.1) play critical presynaptic and postsynaptic roles throughout the nervous system have been implicated in a variety of neurological disorders. Here we report that mice with genetic ablation Ca(v)2.1 pore-forming α(1A) subunit (α(1A)⁻/⁻) encoded by CACNA1a (Jun et al., 1999) suffer during postnatal development from increasing breathing disturbances lead ultimately to death. Breathing abnormalities include decreased minute ventilation specific loss sighs, which was associated lung atelectasis. Similar respiratory alterations were preserved isolated vitro brainstem slice preparation containing pre-Botzinger complex. The an alteration functional dependency on N-type (Ca(v)2.2). Blocking conotoxin GVIA had only minor effects activity slices control (CT) littermates, but abolished all α(1A)⁻/⁻ mice. amplitude evoked EPSPs smaller inspiratory neurons compared CTs. Conotoxin mice, while EPSP reduced 30% CT Moreover, neuromodulation significantly altered as muscarine network not We conclude excitatory synaptic transmission dependent is required for stable sighing. In absence channels, breathing, sighing, are severely compromised, leading early mortality.