Publications (85) View all
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Article: Foreword.
Respiratory Physiology & Neurobiology 10/2012; · 2.24 Impact Factor -
Article: Carotid chemoreceptor "resetting" revisited.
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ABSTRACT: Carotid body (CB) chemoreceptors transduce low arterial O(2) tension into increased action potential activity on the carotid sinus nerves, which contributes to resting ventilatory drive, increased ventilatory drive in response to hypoxia, arousal responses to hypoxia during sleep, upper airway muscle activity, blood pressure control and sympathetic tone. Their sensitivity to O(2) is low in the newborn and increases during the days or weeks after birth to reach adult levels. This postnatal functional maturation of the CB O(2) response has been termed "resetting" and it occurs in every mammalian species studied to date. The O(2) environment appears to play a key role; the fetus develops in a low O(2) environment throughout gestation and initiation of CB "resetting" after birth is modulated by the large increase in arterial oxygen tension occurring at birth. Although numerous studies have reported age-related changes in various components of the O(2) transduction cascade, how the O(2) environment shapes normal CB prenatal development and postnatal "resetting" remains unknown. Viewing CB "resetting" as environment-driven (developmental) phenotypic plasticity raises important mechanistic questions that have received little attention. This review examines what is known (and not known) about mechanisms of CB functional maturation, with a focus on the role of the O(2) environment.Respiratory Physiology & Neurobiology 09/2012; · 2.24 Impact Factor -
Article: Purinergic modulation of carotid body glomus cell hypoxia response during postnatal maturation in rats.
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ABSTRACT: Carotid body (CB) glomus cells respond to hypoxia by releasing neurotransmitters, such as ATP, which are believed to stimulate excitatory receptors on apposed nerve endings of the carotid sinus nerves as well as bind to autoreceptors on the glomus cell membrane to modulate response magnitude. The CB response to hypoxia is small at birth and increases during postnatal maturation in mammals. As ATP has been shown to inhibit the glomus cell response to hypoxia via an autoreceptor mechanism, we hypothesized that ATP-mediated inhibition may vary with age and play a role in postnatal development of the hypoxia response magnitude. The effects of ATP on CB glomus cell intracellular calcium ([Ca(2+)](i)) responses to hypoxia were studied at two ages, P0-1 and P14-18. The inhibitory effect of ATP or a stable ATP analog on the glomus cell response to hypoxia was greater in newborn rats compared to the more mature age group. Use of selective P2Y receptor agonists and antagonists suggests that the inhibitory effect of ATP on the glomus cell [Ca(2+)](i) response to hypoxia may be mediated by a P2Y12 receptor. Thus, developmental changes in ATP-mediated glomus cell inhibition may play a role in carotid chemoreceptor postnatal maturation.Advances in experimental medicine and biology 01/2012; 758:249-53. · 1.09 Impact Factor -
Article: Postnatal hyperoxia impairs acute oxygen sensing of rat glomus cells by reduced membrane depolarization.
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ABSTRACT: Previous work demonstrated that hyperoxia (30-60% O(2)) exposure in the post-natal period reduces the ventilatory response to acute hypoxia and this impairment may continue considerably beyond the period of hyperoxia exposure. Previous work from our laboratory demonstrated that 1-2 weeks of hyperoxia (60% O(2)) starting between P1 and P14: reduced the single chemoreceptor unit response to hypoxia, reduced the rise in glomus cell calcium caused by acute hypoxia and reduced hypoxia-induced catecholamine release (Donnelly 05, Donnelly 09). The present study asked whether the impairment extended to hypoxia-induced membrane depolarization, an earlier step in the transduction cascade. Perforated patch, whole-cell recordings were obtained from rat glomus cells exposed to hyperoxia from P0-P8 or P8-P15 and age-matched control groups. In both cases, hypoxia-induced membrane depolarization was significantly less in the hyperoxia treated groups compared to controls, while depolarization to 20 mM K(+) was not significantly affected. Resting membrane potential and input resistance were also not different in the hyperoxia treated groups. Whole carotid body quantitative real time PCR showed that TASK-1, TASK-3 and L-type Ca(2+) channel expression was significantly down-regulated at Hyper 8-15 compared to controls. We conclude that 1 week of postnatal hyperoxia during the early and late stage of CB maturation impairs organ function by affecting the coupling between hypoxia and glomus cell depolarization. This may be caused by altered expression of TASK1, TASK3 or L-type Ca(2+) channel gene expression. We speculate that an identification of cellular changes caused by hyperoxia may yield unique insights to the mechanism of oxygen sensing by the carotid bodies.Advances in experimental medicine and biology 01/2012; 758:49-54. · 1.09 Impact Factor -
Article: Periodic limb movements during sleep in children with narcolepsy.
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ABSTRACT: In adults with narcolepsy, periodic limb movements of sleep (PLMS) occur more frequently than in control population, and presence of increased PLMS is associated with greater sleep disruption and shorter mean sleep latency. This study was performed to determine whether PLMS are common in children with narcolepsy, and whether the presence of PLMS is associated with greater sleep disruption. Demographic and polysomnographic information were collected from consecutive patients diagnosed with narcolepsy identified retrospectively by diagnosis-based search. Descriptive data were compiled, and sleep characteristics of children with and without PLMS were compared. Sleep disorders center in a children's hospital. 44 patients, 6-19 years old (mean 13 years, SD 3.57), were identified. Twenty-eight were African American. None. Four patients had a PLMS index (PLMI) ≥ 5/h (considered abnormal in literature). Sixteen (36%) had "any PLMS" (PLMI > 0/h). The mean PLMI was 1.3/h (SD 2.5). Sleep was significantly more disrupted, and the mean sleep latency was shorter in patients with "any PLMS" as compared to those with no PLMS. There was no correlation between the PLMI and other diagnostic criteria for narcolepsy. "Any PLMS" were present equally in children of African American and Caucasian heritage, 35.7% vs. 37.5%. As in adults, children with PLMS and narcolepsy have more sleep disruption and shorter mean sleep latencies than those with narcolepsy but without PLMS. Our findings also suggest that the use of adult criteria for diagnosis of "significant" PLMS in children may not be sufficiently sensitive.Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 12/2011; 7(6):597-601. · 3.23 Impact Factor
