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.
| Lahiri, S; Mitchell, C H; Reigada, D et al. (2007) Purines, the carotid body and respiration. Respir Physiol Neurobiol 157:123-9 |
| Lahiri, S; Roy, A; Baby, S M et al. (2006) Oxygen sensing in the body. Prog Biophys Mol Biol 91:249-86 |
| Lahiri, S; Roy, A; Li, J et al. (2004) Role of Fe2+ in oxygen sensing in the carotid body. Adv Exp Med Biol 551:59-64 |
| Roy, Arijit; Li, Jingqing; Baby, Santhosh M et al. (2004) Effects of iron-chelators on ion-channels and HIF-1alpha in the carotid body. Respir Physiol Neurobiol 141:115-23 |
| Lahiri, Sukhamay; Roy, Arijit; Li, Jinquing et al. (2003) Ca2+ responses to hypoxia are mediated by IP3-R on Ca2+ store depletion. Adv Exp Med Biol 536:25-32 |
| Di Giulio, C; Huang, W X; Mokashi, A et al. (2003) Sustained hypoxia promotes hyperactive response of carotid body in the cat. Respir Physiol Neurobiol 134:69-74 |
| Mokashi, A; Li, J; Roy, A et al. (2003) ATP causes glomus cell [Ca2+]c increase without corresponding increases in CSN activity. Respir Physiol Neurobiol 138:1-18 |
| Baby, Santhosh M; Roy, Arijit; Mokashi, Anil M et al. (2003) Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1alpha and -1beta in the rat carotid body and glomus cells. Histochem Cell Biol 120:343-52 |
| Lahiri, Sukhamay; Di Giulio, Camillo; Roy, Arijit (2002) Lessons from chronic intermittent and sustained hypoxia at high altitudes. Respir Physiol Neurobiol 130:223-33 |
| Li, Jinqing; Roy, Arijit; Mokashi, Anil et al. (2002) CO-induced K(+) currents in rat glomus cells are insensitive to light unlike carotid body neural discharge and Vo(O(2)). Respir Physiol Neurobiol 131:285-90 |
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