Abstract
The locus coeruleus (LC) contains noradrenergic neurons that are innervated by orexin (ORX)-like immunoreactive axons and express both orexin receptor-1 and -2. We studied effects of ORX-A and -B (ORX-A/B) on dissociated LC neurons by using whole-cell patch clamp techniques. In current-clamp mode, LC neurons were depolarized by application of ORX-A (10(-7) M) [53% of neurons tested; 9.0+/-0.2 mV (n=5)], or ORX-B (10(-7) M) [38% of neurons tested; 4.0+/-0.1 mV (n=5)]. Firing frequencies of action potentials increased during application [1.1+/-0.2 Hz (n=5) in ORX-A; 0.8+/-0.2 Hz (n=5) in ORX-B] and returned to the control level [0.2+/-0.1 Hz (n=5)] after removal. The ORX-A/B-induced depolarization was well maintained in the presence of TTX (3x10(-7) M), CNQX (10(-6) M) and AP5 (10(-5) M). In voltage-clamp mode, removal of external Na+ suppressed both ORX-A/B-induced currents and shifted their reversal potentials from approximately -45 mV to -60 mV. In addition, ORX-A/B inhibited sustained K+ currents. These results suggest that ORX-A/B increase the firing frequency of LC neurons through the depolarization probably produced by both augmentation of the nonselective cationic conductance and inhibition of the sustained K+ conductance.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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4-Aminopyridine / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Analysis of Variance
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Animals
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Animals, Newborn
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Interactions
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Electric Stimulation / methods
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Excitatory Amino Acid Antagonists / pharmacology
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Intracellular Signaling Peptides and Proteins / classification
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Intracellular Signaling Peptides and Proteins / pharmacology*
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Ion Channels / drug effects
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Ion Channels / metabolism
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Locus Coeruleus / cytology*
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Membrane Potentials / drug effects
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Neurons / drug effects*
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Neurons / radiation effects
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Neuropeptides / classification
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Neuropeptides / pharmacology*
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Orexins
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Patch-Clamp Techniques / methods
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Potassium Channel Blockers / pharmacology
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Potassium Channels / drug effects
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Potassium Channels / metabolism*
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Rats
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Rats, Wistar
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Sodium Channel Blockers / pharmacology
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Tetraethylammonium / pharmacology
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Tetrodotoxin / pharmacology
Substances
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Excitatory Amino Acid Antagonists
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Intracellular Signaling Peptides and Proteins
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Ion Channels
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Neuropeptides
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Orexins
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Potassium Channel Blockers
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Potassium Channels
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Sodium Channel Blockers
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Tetrodotoxin
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Tetraethylammonium
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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4-Aminopyridine