Postsynaptic mechanisms of CO(2) responses in parafacial respiratory neurons of newborn rats.
The parafacial respiratory group (pFRG) in the rostral ventrolateral medulla of the newborn rat is predominantly composed of pre-inspiratory (Pre-I) neurons and is involved in respiratory rhythm generation. The subgroup located close to the ventral surface (at least partially overlapping the retrotrapezoid nucleus, RTN) expresses the Phox2b transcription factor and responds to hypercapnic stimulation with strong depolarization, which suggests it has a role in central chemoreception. Although a CO(2) response of pFRG/RTN neurons has been confirmed in the presence of tetrodotoxin (TTX), it is unknown whether the depolarization involved in this response is induced by a direct postsynaptic response of pFRG/RTN neurons or by any presynaptic components mediated by Ca(2+)-dependent mechanisms. In this study, we examined the effects of ATP or substance P receptor antagonists on hypercapnic responses of rostral pFRG/RTN neurons. We tested effects of Cd(2+) and low Ca(2+)-high Mg(2+) in the presence of TTX. The experiments were performed in in vitro brainstem–spinal cord preparations from newborn rats in which Pre-I neurons reflect the discharge pattern of the pFRG. We found that ATP receptor and substance P receptor antagonists do not block membrane potential responses to hypercapnic stimulation (2%→8%) of pFRG/RTN neurons in the rostral parafacial region.Moreover, rostral pFRG/RTN neurons were depolarized by hypercapnia under conditions where the contribution of presynaptic components was inhibited in the presence of TTX and Cd(2+) or in a low Ca(2+)-high Mg(2+) solution containing TTX and Cd(2+). All cases (except some cases in a low Ca(2+)-high Mg(2+) solution) of membrane depolarization by hypercapnic stimulation were accompanied with an increase in input resistance. These neurons were predominantly Phox2b immunoreactive. Our findings suggest that the response of pFRG/RTN neurons to hypercapnia is induced by direct action on the postsynaptic membrane via closing of K(+) channels.
Department of Physiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan. oni@med.showa-u.ac.jp
Hiroshi
H
Onimaru
Keiko
K
Ikeda
Kiyoshi
K
Kawakami
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002245:Carbon Dioxide / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D006935:Hypercapnia / Q000503:physiopathology; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*
D002121:Calcium Channel Blockers; D018398:Homeodomain Proteins; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C109220:NBPhox protein; D064729:Neurokinin-1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018048:Receptors, Purinergic P2; D014157:Transcription Factors; D002104:Cadmium; D002245:Carbon Dioxide; C076851:L 703606; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D013373:Substance P; D013779:Tetrodotoxin; D011732:Pyridoxal Phosphate; D000244:Adenosine Diphosphate; C042867:spantide; D008274:Magnesium; D002118:Calcium