'Hypoxic ventilatory decline' in the intracellular Ca2+ response to sustained isocapnic hypoxia in carotid body glomus cells.
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 Ca(2+) 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% CO(2) in N(2)), asphyxia (20% CO(2) in N(2)), hypercapnia (20% CO(2) in air), 100 mM K+ and 2 mM Ba(2+). Intracellular Ca(2+) transients [Ca(2+)]i were measured using indo-1 dye. Hypoxia elicited rapid increase in [Ca(2+)]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 [Ca(2+)]i responses displayed a more rapid initial decline (within 2- min) but then stabilised. Exposure to Ba(2+) evoked characteristic spiking activity in the [Ca(2+)]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 [Ca(2+)]i in a manner akin to HVD.
Pandit
Jaideep J
JJ
Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford, UK. jaideep.pandit@dpag.ox.ac.uk
Collyer
Josie
J
Buckler
Keith J
KJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002344:Carotid Body / Q000166:cytology* / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D042541:Intracellular Space / Q000378:metabolism*; D012123:Pulmonary Ventilation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002118:Calcium