RESUMO
In order to examine whether ATP-sensitive potassium channel Kir6.2 is involved in hypoxic ventilatory responses, especially in hypoxic ventilatory depression (HVD), and whether the involvement shows age-dependence, we measured the hypoxic ventilatory response in the Kir6.2-knockout mouse (Kir6.2-/-) in an unanesthetized unrestrained state by means of pressure plethysmography in the 2nd and 4th postnatal weeks, and compared the response with that of its wild type counterpart, the C57BL6/J mouse. In the 4th postnatal week, but not in the 2nd week, the Kir6.2-/- exhibited a larger and longer initial augmentation and a weaker subsequent depression of respiratory frequency and ventilation in response to hypoxia (FIO(2)=0.12 in N(2)). These findings suggest that Kir6.2 is involved in HVD of the mouse at a certain point during the postnatal development.
Assuntos
Trifosfato de Adenosina/fisiologia , Envelhecimento/fisiologia , Hipóxia , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Ventilação Pulmonar/fisiologia , Trifosfato de Adenosina/farmacologia , Análise de Variância , Animais , Animais Recém-Nascidos , Peso Corporal/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxigênio/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/deficiência , Ventilação Pulmonar/efeitos dos fármacos , Fatores de TempoAssuntos
Canais de Potássio/fisiologia , Fenômenos Fisiológicos Respiratórios , Animais , Tronco Encefálico/fisiologia , Células Quimiorreceptoras/fisiologia , Técnicas In Vitro , Camundongos , Camundongos Knockout , Oxigênio/metabolismo , Canais de Potássio/deficiência , Canais de Potássio/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Medula Espinal/fisiologiaRESUMO
In order to determine the role of Kir2.2 in the hypercapnic ventilatory response (HCVR) during postnatal development, we measured the response of the Kir2.2-knockout (Kir2.2-/-) mouse in an unanesthetized unrestrained state by means of pressure plethysmography on postnatal days 9-10, 14-15 and 18, and compared the response with that in its wild counterpart, the FVB mouse. We also examined developmental changes in m-RNA expression of Kir2.2 in the brainstem of the FVB mouse using quantitative real-time PCR assay. Kir2.2-/- exhibited a smaller increase in tidal volume and minute ventilation volume than the FVB mouse in response to hypercapnic challenge on days 14-15. Meanwhile, the FVB mouse showed a transient increase in m-RNA expression of Kir2.2 in the brainstem on days 14-15. These findings suggest that Kir2.2 in the brainstem plays a transient role in HCVR, possibly through central ventilatory chemosensitivity, during postnatal development.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Hipercapnia/fisiopatologia , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Respiração , Fatores Etários , Análise de Variância , Animais , Southern Blotting/métodos , Tronco Encefálico/crescimento & desenvolvimento , Tronco Encefálico/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Genótipo , Hipercapnia/genética , Camundongos , Camundongos Knockout , Fenótipo , Pletismografia/métodos , Canais de Potássio Corretores do Fluxo de Internalização/deficiência , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Volume de Ventilação Pulmonar/genética , Vigília/fisiologiaRESUMO
We examined the effects of pharmacological inactivation and electrical stimulation of the locus coeruleus (LC) on the respiratory rate (RR) in isolated brainstem-spinal cord preparations of the neonatal rat. The brainstem and spinal cord were isolated en bloc from neonatal (days 1-4) Sprague-Dawley rats and superfused with artificial cerebrospinal fluid (ACSF) equilibrated with a gas mixture containing 2% CO(2) (pH 7.8). Pharmacological inactivation of the bilateral LC by means of microinjection of tetrodotoxin or noradrenaline elicited a significant decrease in RR in preparations obtained from rats aged 3-4 days, but not in preparations of rats aged 1-2 days. Stimulation of the bilateral LC with a train of electrical pulses (25-50 microA, 30 ms, 0.5 Hz, 3-4 min) caused a marginal but significant increase in RR on days 3-4, but not on days 1-2. These results indicate that the LC exerts an excitatory effect on the medullary respiratory rhythm generator in an age-dependent manner.
