| First Author | Koch H | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 8 | Pages | 3633-45 |
| PubMed ID | 23426690 | Mgi Jnum | J:195984 |
| Mgi Id | MGI:5486372 | Doi | 10.1523/JNEUROSCI.6390-11.2013 |
| Citation | Koch H, et al. (2013) Stable respiratory activity requires both P/Q-type and N-type voltage-gated calcium channels. J Neurosci 33(8):3633-45 |
| abstractText | P/Q-type voltage-gated calcium channels (Ca(v)2.1) 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 Ca(v)2.1 pore-forming alpha(1A) subunit (alpha(1A)(-)/(-)) 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 isolated in vitro brainstem slice preparation containing the pre-Botzinger complex. The loss of Ca(v)2.1 was associated with an alteration in the functional dependency on N-type calcium channels (Ca(v)2.2). 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 alpha(1A)(-)/(-) mice. The amplitude of evoked EPSPs was smaller in inspiratory neurons from alpha(1A)(-)/(-) mice compared with CTs. Conotoxin GVIA abolished all EPSPs in inspiratory neurons from alpha(1A)(-)/(-) 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 alpha(1A)(-)/(-) 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. |
