Resetting and postnatal maturation of oxygen chemosensitivity in rat carotid chemoreceptor cells

Autor: Laura M. Sterni, John L. Carroll, O. S. Bamford, M. J. Wasicko, Marshall H. Montrose
Rok vydání: 1998
Předmět:
Zdroj: The Journal of physiology. 514
ISSN: 0022-3751
Popis: Regulation of arterial oxygen levels is critically important in mammals, particularly during early life. Peri- and postnatal hypoxia may lead to impaired cognitive development, abnormalities in cardiovascular function, breathing control maturation and lung function, and death (Okubo & Mortola, 1988; Nyakas et al. 1996; Hudlicka & Brown, 1996). The main sensors of arterial O2 tension are the carotid body chemoreceptors, which are located bilaterally at the bifurcations of the common carotid arteries. Carotid chemoreceptor sensory afferents, via the carotid sinus nerves (CSN), project to the nucleus tractus solitarii and other brainstem nuclei, providing the major source of O2-mediated ventilatory drive. Neural signals from the carotid chemoreceptors to brainstem cardiorespiratory control nuclei also mediate critically important respiratory reflexes such as arousal from sleep during hypoxia and cardiovascular reflexes that modulate heart rate and blood pressure (Marshall, 1987). The primary site of oxygen sensing in the carotid body is thought to be the type I cell (Gonzalez et al. 1994). Type I cells are specialized sensory neurons which depolarize in response to low O2, resulting in Ca2+ entry via voltage-gated calcium channels, and exocytosis of neurotransmitters and modulators onto apposed CSN terminals (Gonzalez et al. 1994). Although further study is needed to define their precise role, there is little question that type I cells play a crucial role in carotid chemoreceptor oxygen sensing. Carotid denervation, which is well tolerated by adults, in neonates leads to profound abnormalities of respiratory control and high mortality rates. In piglets and in lambs the effects of carotid denervation just after birth are not immediate but, instead, life-threatening respiratory abnormalities occur weeks later (Bureau et al. 1985; Donnelly & Haddad, 1990; Cote et al. 1996). This suggests a ‘vulnerable period’ during mammalian postnatal maturation, during which functioning carotid chemoreceptors become essential for surviving infancy. Perhaps surprisingly, given their obvious importance, the carotid chemoreceptors are minimally sensitive just after birth and become active over the next few days. Previous studies suggest a slower phase of carotid chemoreceptor maturation, with O2 sensitivity increasing slowly over weeks or months (Carroll et al. 1993). This rightward shifting of the O2 response range after birth is termed ‘resetting’ of the arterial chemoreceptors and it occurs in both the carotid and aortic chemoreceptors (Kumar & Hanson, 1989). Although it is clear that oxygen tension at birth is the major factor modulating carotid chemoreceptor resetting (Blanco et al. 1988), the mechanism and site of resetting are unknown. Using fura-2 to measure intracellular calcium ([Ca2+]i), we previously reported that enzymatically isolated type I cells of the newborn rabbit exhibit smaller [Ca2+]i responses to hypoxia compared with cells isolated from adults and studied under identical conditions (Sterni et al. 1995). However, our previous study examined only two ages, 1-2 days old vs. adult, and one level of hypoxia. Maturation of type I cell [Ca2+]i responses to graded hypoxia and the developmental profile of O2 sensitivity resetting have not been reported. In addition, it is not known whether the peri- and postnatal development of type I cell [Ca2+]i responses involves the development of mechanisms leading to cell depolarization or whether they reflect an age-related increase in the [Ca2+]i rise resulting from depolarization. If postnatal resetting and maturation of carotid chemoreceptor O2 sensitivity reflects properties of the type I cell, then type I cell O2 sensitivity should be low at the time of birth and increase postnatally with a profile consistent with the known time course of carotid chemoreceptor maturation. The present study aimed to determine the developmental profile of [Ca2+]i responses to maximal and submaximal hypoxic stimulation, the developmental profile of type I cell sensitivity to graded hypoxia, and the dependence of [Ca2+]i responses to elevated extracellular K+ on the level of postnatal maturity.
Databáze: OpenAIRE
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