A neuronal mechanism of propofol-induced central respiratory depression in newborn rats.
The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.
*Department of Anesthesiology, School of Medicine, Keio University; †Department of Physiology, Teikyo University School of Medicine, Tokyo; and ‡Department of Medicine, Keio University Tsukigase Rehabilitation Center, Shizuoka-ken, Japan.
Masanori
M
Kashiwagi
Yasumasa
Y
Okada
Shun-Ichi
SI
Kuwana
Shigeki
S
Sakuraba
Ryoichi
R
Ochiai
Junzo
J
Takeda
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D002492:Central Nervous System Depressants; D003864:Depression, Chemical; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D018686:Anesthetics, Intravenous; D002492:Central Nervous System Depressants; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D001640:Bicuculline; D015742:Propofol