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Mu opioid receptors hyperpolarize respiratory‐controlling Kölliker‐Fuse neurons (712.1)
Author(s) -
Levitt Erica,
Abdala Ana,
Paton Julian,
Bissonnette John,
Williams John
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.712.1
Subject(s) - damgo , g protein coupled inwardly rectifying potassium channel , agonist , desensitization (medicine) , (+) naloxone , chemistry , pharmacology , yohimbine , opioid , μ opioid receptor , opioid receptor , rostral ventrolateral medulla , receptor , anesthesia , medicine , antagonist , medulla oblongata , g protein , central nervous system
Respiratory depression is the primary cause of death from opioid overdose, yet little is known about the cellular mechanisms of opioids on respiratory‐controlling neurons. The pontine Kölliker‐Fuse (KF) regulates respiration, especially the inspiratory/expiratory phase transition. In the in situ arterially perfused working heart‐brainstem preparation of rat, injection of the mu opioid agonist DAMGO into the KF caused robust apneusis that was similar to complete silencing of the KF. The apneusis was rapidly reversed by perfusion of the opioid antagonist naloxone. In whole‐cell recordings from KF neurons contained in rat brain slices, activation of mu opioid receptors hyperpolarized a majority (75%) of KF neurons. The hyperpolarizing current produced by [Met5]enkephalin (ME) was concentration‐dependent, reversed at the potassium equilibrium potential and was blocked by BaCl2, characteristics of a GIRK conductance. Unexpectedly, the partial agonist morphine produced the same amplitude current as full agonists DAMGO or ME, indicating a large receptor reserve. The presence of many spare receptors could reduce the degree of desensitization induced by prolonged application of ME. Indeed, only minimal acute desensitization of the ME‐mediated GIRK current was observed. This lack of desensitization correlates with the lack of tolerance to the respiratory depressant effects of opioids. Grant Funding Source : Supported by DA08163 (JTW) and DA33036 (ESL)