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Respiration‐modulated membrane potential and chemosensitivity of locus coeruleus neurones in the in vitro brainstem‐spinal cord of the neonatal rat
Author(s) -
Oyamada Y.,
Ballantyne D.,
Mückenhoff K.,
Scheid P.
Publication year - 1998
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 - 10.1111/j.1469-7793.1998.381bb.x
Subject(s) - cnqx , depolarization , locus coeruleus , excitatory postsynaptic potential , chemistry , idazoxan , hyperpolarization (physics) , brainstem , endocrinology , inhibitory postsynaptic potential , medicine , spinal cord , anesthesia , antagonist , receptor , biology , glutamate receptor , central nervous system , neuroscience , biochemistry , prazosin , ampa receptor , stereochemistry , nuclear magnetic resonance spectroscopy
1 The activity of locus coeruleus (LC) neurones ( n = 126 ) was examined in whole‐cell (conventional and amphotericin B‐perforated patch) recordings, and the relationship of this activity to the respiratory discharge recorded on the C4 or C5 phrenic nerve roots was determined at different CO 2 concentrations (2 and 8 %; bath pH 7.8 and 7.2) in the in vitro brainstem‐spinal cord preparation of the neonatal rat (1–5 days old). 2 In most neurones ( n = 105 ) ongoing activity was modulated at respiratory frequency. Typically, this consisted of a phase of depolarization and increased discharge frequency synchronous with the phrenic burst, followed by a phase of hyperpolarization and inhibition of discharge ( n = 94 of 105 ). The incidence of respiratory modulation decreased from 91 % on P1 to 57 % on P5. 3 Bath application of the non‐n m DA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; 5 μm m u; m ) or the n m DA receptor antagonist DL‐2‐amino‐5‐phosphonovaleric acid (APV; 100 μm m u; m ) abolished both phases of respiratory modulation. The hyperpolarizing phase alone was abolished by the adrenoceptor antagonists idazoxan (5 μm m u; m ) or phentolamine (0.8 μm m u; m ). These results indicate that excitatory amino acid pathways are involved in the transmission of both the excitatory and inhibitory components and that the latter involves in addition an α 2 ‐adrenoceptor‐mediated pathway. 4 Increasing the CO 2 concentration from 2 to 8 % resulted in a shortening of expiratory duration and weakening or loss of respiratory‐phased inhibition; this was accompanied by depolarization, increased discharge frequency and, in those neurones where they were initially present (60 %), an increase in the frequency of subthreshold membrane potential oscillations. The depolarizing response was retained in the presence of tetrodotoxin (TTX, 0.2–1.0 μm m u; m ). 5 These results indicate that in this neonatal preparation LC neurones form part of the synaptically connected brainstem respiratory network, and that the LC constitutes a site of CO 2 ‐ or pH‐dependent chemoreception.