PERIPHERAL CHEMORECEPTORS: MECHANISMS &MODULATIONS

University Of Pennsylvania, Philadelphia PA

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Abstract

The long range goal is to understand the cellular basis of chemoreception in carotid bodies in adult animals. However, the cellular basis is uncertain. The conventional wisdom is that glomus cells (type I) are the sensors. They along with the only afferents which are connected with these cells form the chemoreceptor unit. The membrane (ionic) model involves inhibition of K+ channels by hypoxia and hypercapnia, leading to depolarization of glomus cells, consequent activation of voltage- gated channels and hence Ca2+ influx, triggering neurosecretion and neural discharge. There is considerable difference in ionic responses between the three species. Yet the chemosensory responses are presumably the same. This proposal challenges the concept of K+ currents suppression leading to subsequent events. [Ca2+]i may be the key element in the cascade of events. The specific aims are: (1) to quantitate the cellular interactions of responses of [Ca2+]I and the sensory afferents to hypoxia and hypercapnia; (2) to test and challenge the hypothesis that K+- current is key to hypoxic and hypercapnic interactions; (3) to test whether the mechanisms CO2-H+ response are different from hypoxic responses and to discriminate between the contribution of intracellular and extracellular calcium to increase in cytosolic Ca2+. To understand the species differences in the K+ current responses with the same chemosensory responses, we wish to study three adult male species: rats, cat and rabbit. In vitro chemosensory discharges of perfused and superfused carotid bodies of adult rat, cat and rabbit carotid bodies and [Ca2+]i of glomus cells of the same species are the key measurements in the assessment of our hypothesis. The other measurements include tissue PO2 and dopamine release. Adequate supply of O2 and concomitant CO2 removal are essential for survival of mammalian species. In that survival, one of the first steps in acute hypoxia is to increase pulmonary ventilation through the mediation of carotid bodies and increased chemosensory discharge. The aim of this proposal is to understand how the processes are initiated in the chemosensory cells.