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Role of persistent sodium current in mouse preBötzinger Complex neurons and respiratory rhythm generation
Author(s) -
Pace Ryland W.,
Mackay Devin D.,
Feldman Jack L.,
Del Negro Christopher A.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.124602
Subject(s) - microinjection , tetrodotoxin , depolarization , nap , respiratory system , neuroscience , biology , cnqx , biophysics , sodium channel , rhythm , serotonergic , chemistry , raphe nuclei , microbiology and biotechnology , medicine , serotonin , anatomy , sodium , biochemistry , receptor , glutamate receptor , ampa receptor , organic chemistry
Breathing movements in mammals depend on respiratory neurons in the preBötzinger Complex (preBötC), which comprise a rhythmic network and generate robust bursts that form the basis for inspiration. Persistent Na + current ( I NaP ) is widespread in the preBötC and is hypothesized to play a critical role in rhythm generation because of its subthreshold activation and slow inactivation properties that putatively promote long‐lasting burst depolarizations. In neonatal mouse slice preparations that retain the preBötC and generate a respiratory‐related rhythm, we tested the role of I NaP with multiple Na + channel antagonists: tetrodotoxin (TTX; 20 n m ), riluzole (RIL; 10 μ m ), and the intracellular Na + channel antagonist QX‐314 (2 m m ). Here we show that I NaP promotes intraburst spiking in preBötC neurons but surprisingly does not contribute to the depolarization that underlies inspiratory bursts, i.e. the inspiratory drive potential. Local microinjection in the preBötC of 10 μ m RIL or 20 n m TTX does not perturb respiratory frequency, even in the presence of bath‐applied 100 μ m flufenamic acid (FFA), which attenuates a Ca 2+ ‐activated non‐specific cation current ( I CAN ) that may also have burst‐generating functionality. These data contradict the hypothesis that I NaP in preBötC neurons is obligatory for rhythmogenesis. However, in the presence of FFA, local microinjection of 10 μ m RIL in the raphe obscurus causes rhythm cessation, which suggests that I NaP regulates the excitability of neurons outside the preBötC, including serotonergic raphe neurons that project to, and help maintain, rhythmic preBötC function.