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This Article Full Text Full Text (PDF) All Versions of this Article: 584/1/149    most recent jphysiol.2007.132274v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Carabelli, V. Articles by Carbone, E. Search for Related Content PubMed PubMed Citation Articles by Carabelli, V. Articles by Carbone, E. Related Collections Neuroscience

¹ Department of Neuroscience, NIS Center of Excellence, CNISM Research Unit,10125 Torino, Italy
² Department of Physical Medicine and Pharmacology, University de La Laguna, 38071 La Laguna, Spain

_1H T-type channels recruited by ₁-adrenergic stimulation in rat chromaffin cells (RCCs) are coupled to fast exocytosis with the same Ca²⁺ dependence of high-threshold Ca²⁺ channels. Here we show that RCCs exposed to chronic hypoxia (CH) for 12–18 h in 3% O₂ express comparable densities of functional T-type channels that depolarize the resting cells and contribute to low-voltage exocytosis. Following chronic hypoxia, most RCCs exhibited T-type Ca²⁺ channels already available at –50 mV with the same gating, pharmacological and molecular features as the _1H isoform. Chronic hypoxia had no effects on cell size and high-threshold Ca²⁺ current density and was mimicked by overnight incubation with the iron-chelating agent desferrioxamine (DFX), suggesting the involvement of hypoxia-inducible factors (HIFs). T-type channel recruitment occurred independently of PKA activation and the presence of extracellular Ca²⁺. Hypoxia-recruited T-type channels were partially open at rest (T-type ‘window-current’) and contributed to raising the resting potential to more positive values. Their block by 50 µM Ni²⁺ caused a 5–8 mV hyperpolarization. The secretory response associated with T-type channels could be detected following mild cell depolarizations, either by capacitance increases induced by step depolarizations or by amperometric current spikes induced by increased [KCl]. In the latter case, exocytotic bursts could be evoked even with 2–4 mM KCl and spike frequency was drastically reduced by 50 µM Ni²⁺. Chronic hypoxia did not alter the shape of spikes, suggesting that hypoxia-recruited T-type channels increase the number of secreted vesicles at low voltages, without altering the mechanism of catecholamine release and the quantal content of released molecules.

(Received 14 March 2007; accepted after revision 3 August 2007; first published online 9 August 2007)
Corresponding author E. Carbone: Department of Neuroscience, Corso Raffaello 30, 10125 Torino, Italy. Email: emilio.carbone{at}unito.it