Stable respiratory activity requires both P/Q-type and N-type voltage-gated calcium channels
| Autor: | Lincoln S. Smith, Atsushi Doi, Henner Koch, Sebastien Zanella, Gina E. Elsen, Robert F. Hevner, Jan-Marino Ramirez, Sarah Kirsch, Christopher M. Gomez, Randy Xun, Aguan D. Wei, Alfredo J. Garcia |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty P-type calcium channel Mice 129 Strain Biology Article Calcium Channels Q-Type chemistry.chemical_compound Mice Slice preparation Calcium Channels N-Type Organ Culture Techniques Neuromodulation Internal medicine medicine Animals Respiratory system Mice Knockout Muscarine Voltage-dependent calcium channel General Neuroscience T-type calcium channel Excitatory Postsynaptic Potentials Calcium Channels P-Type Endocrinology medicine.anatomical_structure chemistry Animals Newborn Anesthesia Excitatory postsynaptic potential Respiratory Mechanics Female Brain Stem |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(8) |
| ISSN: | 1529-2401 |
| Popis: | P/Q-type voltage-gated calcium channels (Cav2.1) play critical presynaptic and postsynaptic roles throughout the nervous system and have been implicated in a variety of neurological disorders. Here we report that mice with a genetic ablation of the Cav2.1 pore-forming α1Asubunit (α1A−/−) encoded by CACNA1a (Jun et al., 1999) suffer during postnatal development from increasing breathing disturbances that lead ultimately to death. Breathing abnormalities include decreased minute ventilation and a specific loss of sighs, which was associated with lung atelectasis. Similar respiratory alterations were preserved in the isolatedin vitrobrainstem slice preparation containing the pre-Bötzinger complex. The loss of Cav2.1 was associated with an alteration in the functional dependency on N-type calcium channels (Cav2.2). Blocking N-type calcium channels with conotoxin GVIA had only minor effects on respiratory activity in slices from control (CT) littermates, but abolished respiratory activity in all slices from α1A−/−mice. The amplitude of evoked EPSPs was smaller in inspiratory neurons from α1A−/−mice compared with CTs. Conotoxin GVIA abolished all EPSPs in inspiratory neurons from α1A−/−mice, while the EPSP amplitude was reduced by only 30% in CT mice. Moreover, neuromodulation was significantly altered as muscarine abolished respiratory network activity in α1A−/−mice but not in CT mice. We conclude that excitatory synaptic transmission dependent on N-type and P/Q-type calcium channels is required for stable breathing and sighing. In the absence of P/Q-type calcium channels, breathing, sighing, and neuromodulation are severely compromised, leading to early mortality. |
| Databáze: | OpenAIRE |
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