title: Intracellular sodium and calcium homeostasis during hypoxia in dopamine neurons of rat substantia nigra pars compacta.
abstract: We investigated the hypoxia-induced disturbance of cytosolic sodium concentration ([Na+]i) and of cytosolic calcium concentration ([Ca2+]i) in dopamine neurons of the substantia nigra pars compacta in rat midbrain slices, by combining whole cell patch-clamp recordings and microfluorometry. Transient hypoxia (3-5 min) induced an outward current (118.7 +/- 15.1 pA, mean +/- SE; VH = -60 mV). The development of this outward current was associated with an elevation in [Na+]i and in [Ca2+]i. The hypoxia-induced outward current as well as the elevations in [Na+]i and [Ca2+]i were not affected by the ionotropic and metabotropic glutamate receptor antagonists -amino-phosphonovalerate (50 microM), 6nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (10 microM) and S-(alpha)-methyl-4-carboxyphenylglycine (500 microM). Tolbutamide, a blocker of ATP-dependent K+ channels, depressed the hypoxia-induced outward current but did not affect the increases in [Na+]i or [Ca2+]i. Increasing the concentration of ATP in the internal solution from 2 to 10 mM strongly reduced the hypoxia-induced outward current but did not reduce the rise in [Na+]i. Decreasing the concentration of extracellular Na+ to 19.2 mM depressed the hypoxia-induced outward current and resulted in a decrease in resting [Na+]i. Under this condition hypoxia still increased [Na+]i, albeit to levels not exceeding those of resting [Na+]i observed under control conditions. We conclude that 1) a major component of the hypoxia-induced outward current of these cells is caused by a depletion of intracellular ATP in combination with an increase in [Na+]i, 2) that the [Na+]i and [Ca2+]i responses are not mediated by glutamate receptors, 3) that the [Na+]i and [Ca2+]i responses are not depressed by activation of sulfonylurea receptors, and 4) that the rise in [Na+]i induced by short-lasting hypoxia is not due to a ATP depletion-induced failure of Na+ extrusion.
authors.affiliation: Department of Pharmacology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale S. Lucia, 00179 Rome.
authors.forename: E
authors.initials: E
authors.lastname: Guatteo
authors.forename: N B
authors.initials: NB
authors.lastname: Mercuri
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
authors.forename: T
authors.initials: T
authors.lastname: Knöpfel
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005470:Fluorometry; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D012964:Sodium; D002118:Calcium; D004298:Dopamine