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Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells.

Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. Research Abstract Details 

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  • Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. Abstract Text:

    v carabelliV Carabelli,a marcantoniA Marcantoni,v comunanzaV Comunanza,a de lucaA de Luca,j J ,r borgesR Borges,e carboneE Carbone,v carabelliV Carabelli,a marcantoniA Marcantoni,v comunanzaV Comunanza,a de lucaA de Luca,j J ,r borgesR Borges,e carboneE Carbone,

    alpha(1H) T-type channels recruited by beta(1)-adrenergic stimulation in rat chromaffin cells (RCCs) are coupled to fast exocytosis with the same Ca(2+) dependence of high-threshold Ca(2+) channels. Here we show that RCCs exposed to chronic hypoxia (CH) for 12-18 h in 3% O(2) 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 Ca(2+) channels already available at -50 mV with the same gating, pharmacological and molecular features as the alpha(1H) isoform. Chronic hypoxia had no effects on cell size and high-threshold Ca(2+) 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 Ca(2+). 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 microm Ni(2+) 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 microm Ni(2+). 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.

    Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. Publishing Authors By Initials

    v carabelliV Carabelli,a marcantoniA Marcantoni,v comunanzaV Comunanza,a de lucaA de Luca,j J ,r borgesR Borges,e carboneE Carbone,v carabelliV Carabelli,a marcantoniA Marcantoni,v comunanzaV Comunanza,a de lucaA de Luca,j J ,r borgesR Borges,e carboneE Carbone,

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    Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: The Journal of physiology

    VOLUME: 584

    Page Numbers: 149-65

    Journal Abbreviation: J. Physiol. (Lond.)

    ISSN: 0022-3751

    DAY: 9

    MONTH: 08

    YEAR: 2007

    Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. Information

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    LANGUAGE: eng

    NlmUniqueID: 266262

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    Grant and Affiliation Information for Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells.

    AFFILIATION: Department of Neuroscience, NIS Center of Excellence, CNISM Research Unit, 10125 Torino, Italy.

    Country: England

    England Research PublicationEngland Research Publication

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    MEDLINETA: J Physiol

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