title: Calcium release from internal stores is required for the generation of spontaneous hyperpolarizations in dopaminergic neurons of neonatal rats.
abstract: We recently have demonstrated the existence of spontaneous hyperpolarizations in midbrain dopaminergic neurons of neonatal but not adult rats. These events are mediated by the opening of apamin-sensitive K(+) channels after a rise in the intracellular concentration of Ca(2+). They are resistant to tetrodotoxin in most cases and are probably endogenous (i.e., not synaptically activated). Here their mechanism was investigated. Cyclopiazonic acid (10 microM), a specific inhibitor of endoplasmic reticulum Ca(2+) ATPases, reversibly abolished the events. Caffeine, which promotes Ca(2+) release from intracellular stores, had concentration-dependent effects. At 1 mM, it markedly and steadily increased the frequency and the amplitude of the hyperpolarizations. At 10 mM, it induced a transient increase in their frequency followed by their cessation. All these effects were quickly reversible. Ryanodine (10 microM), which decreases the conductance of Ca(2+) release channels, irreversibly blocked the spontaneous hyperpolarizations. Dantrolene (100 microM), a blocker of Ca(2+) release from sarcoplasmic reticulum of striated muscle, did not affect the events. On the other hand, Cd(2+) (100-300 microM), a broad antagonist of membrane voltage-gated Ca(2+) channels, significantly reduced the amplitude and the frequency of the hyperpolarizations. However, when the frequency of the events was increased by 1 mM caffeine, Cd(2+) affected them to a smaller extent, whereas cyclopiazonic acid still abolished them. We conclude that internal stores are the major source of Ca(2+) ions that induce the K(+) channel openings underlying the spontaneous hyperpolarizations of these neurons.
authors.affiliation: Laboratory of Pharmacology, University of Liège, Tour de Pathologie (B23), B-4000 Sart Tilman/Liège 1, Belgium. V.Seutin@ulg.ac.be
authors.forename: V
authors.initials: V
authors.lastname: Seutin
authors.forename: F
authors.initials: F
authors.lastname: Mkahli
authors.forename: L
authors.initials: L
authors.lastname: Massotte
authors.forename: A
authors.initials: A
authors.lastname: Dresse
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D003620:Dantrolene / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D012433:Ryanodine; D001030:Apamin; D002110:Caffeine; D000252:Calcium-Transporting ATPases; D003620:Dantrolene; D002118:Calcium; D004298:Dopamine; C000543:cyclopiazonic acid