Physiological properties of late inspiratory neurons and their possible involvement in inspiratory off-switching in cats.
To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-D-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.
Haji
Akira
A
Department of Pharmacology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. mp04ah@ms.toyama-mpu.ac.jp
Okazaki
Mari
M
Yamazaki
Hiromi
H
Takeda
Ryuji
R
D000200:Action Potentials / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002415:Cats; D003655:Decerebrate State; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000032:analysis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis; D012125:Respiratory Center / Q000166:cytology* / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D005968:Glutamate Decarboxylase; D001640:Bicuculline