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

摘要

class="enumerated" style="list-style-type:decimal">Carotid chemoreceptor sensitivity is minimal immediately after birth and increases with postnatal age. In the present study we have investigated the peri- and postnatal developmental time course of [Ca²⁺]i responses to hypoxia in clusters of type I cells isolated from near-term fetal rats and rats that were 1, 3, 7, 11, 14 and 21 days old, using the Ca²⁺-sensitive fluoroprobe fura-2.In type I cells from all age groups a graded increase in [Ca²⁺]i occurred in response to lowering the PO2 from 150 mmHg to 70, 35, 14, 7, 2 and 0 mmHg. The graded [Ca²⁺]i response to hypoxia was hyperbolic at all ages.Type I cells from rats near-term fetal to 1 day old exhibited small [Ca²⁺]i responses, mainly to the most severe levels of hypoxia. After day 1, an increase in the [Ca²⁺]i responses to submaximal hypoxia stimulation resulted in a rightward shift in the O2 response curve. Using the Δ[Ca²⁺]i between 35 and 2 mmHg PO2 as an index of O2 sensitivity, type I cell O2 sensitivity increased approximately 4- to 5-fold between near-term fetal to 1 day old and 11 to 14 days of age.Exposure to elevated extracellular potassium (10, 20 and 40 mm K⁺) caused a dose-dependent [Ca²⁺]i rise in type I cells from all age groups. There were no age-related changes in [Ca²⁺]i responses to any level of K⁺ between near-term fetal and 21 days.We conclude that the maximal type I cell [Ca²⁺]i response to anoxia, as well as the sensitivity to submaximal hypoxic stimulation, of rats aged from near-term fetal to 21 days depends on the level of postnatal maturity. The lack of an age-related increase in the [Ca²⁺]_i response to elevated K⁺ during the timeframe of maximal development of O₂ sensitivity suggests that resetting involves maturation of O₂ sensing, rather than non-specific developmental changes in the [Ca²⁺]_i rise resulting from depolarization.