Hypoxic ventilatory decline in the intracellular Ca2+ response to sustained isocapnic hypoxia in carotid body glomus cells

Abstract

In humans the ventilatory response to sustained isocapnic hypoxia is biphasic: after an initial rapid rise there follows a steady decline of the next 20-30 min termed hypoxic ventilatory decline (HVD). It is not known whether this secondary phase resides in a reducing activity of the peripheral or the central chemoreflex. We wished to assess if the Ca2+ transient that occurs in glomus cells in response to hypoxia exhibits a form of HVD with sustained hypoxia that parallels the human ventilatory response, or if it exhibits a different response. Glomus cells enzymatically isolated from rat pups were exposed to 10 min sustained hypoxia (5% CO2 in N2), asphyxia (20% CO2 in N2), hypercapnia (20% CO2 in air), 100 mM and 2 mM Ba2+. Intracellular Ca2+ transients [Ca 2+]i were measured using indo-1 dye. Hypoxia elicited rapid increase in [Ca2+]i followed by a gradual persistent decline over 10 min to 50% of the peak value. Asphyxia also elicited a biphasic response, with the acute response twice as great as that for hypoxia and the subsequent decline also twice as large occurring over a similar time course. Hypercapnia-and hyperkalaemia-evoked [Ca2+]i responses displayed a more rapid initial decline (within 2- min) but then stabilised. Exposure to Ba2+ evoked characteristic spiking activity in the [Ca2+]i signal. Although the glomus cell shows some adaptation of response to a variety of stimuli, its response to hypoxia is characterized by a biphasic response with continued secondary decline in [Ca2+]i in a manner akin to HVD. © Springer Science+Business Media, LLC 2010.