Chronic hypoxia up-regulates α1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells

V. Carabelli, A. Marcantoni, V. Comunanza, A. De Luca, J. Díaz, R. Borges, Emilio Carbone

Research output: Contribution to journalArticlepeer-review


α1H T-type channels recruited by β1- 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 α1H 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 m m 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.

Original languageEnglish
Pages (from-to)149-165
Number of pages17
JournalJournal of Physiology
Issue number1
Publication statusPublished - Oct 1 2007

ASJC Scopus subject areas

  • Physiology


Dive into the research topics of 'Chronic hypoxia up-regulates α1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells'. Together they form a unique fingerprint.

Cite this