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Contribution of TASK-Like Potassium Channels to the Enhanced Rat Carotid Body Responsiveness to Hypoxia

  • Fernando C. Ortiz
  • Rodrigo Del Rio
  • Rodrigo Varas
  • Rodrigo IturriagaEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 758)

Abstract

A major hallmark of obstructive sleep apnea is the potentiation of the carotid body (CB) chemosensory response to acute hypoxia, as result of the chronic intermittent hypoxia (CIH) exposition. Several mechanisms have been involved in this CB chemosensory potentiation, but the primary target of CIH remains elusive. In physiological conditions, hypoxia depolarized CB chemoreceptor cells, trigger an increase of intracellular Ca2+, and the subsequent transmitter’s release. Since the depolarization is initiated by the inhibition of a TASK-like K+ channel, we studied if CIH may increase the amplitude of the hypoxic-induced depolarization in the chemoreceptor cells, due to an enhanced inhibition of the TASK-like current.

CBs obtained from adult rats exposed to CIH (5% O2, 12 times/hr for 8 hr/day) for 7 days were acute dissociated, and the membrane potential and TASK-like current were recorded from isolated chemoreceptor cells. Resting membrane properties were not modified by CIH, but the amplitude of the hypoxic-evoked depolarization increases ∼2-fold. The same result was obtained when all the voltage-dependent K+ currents were pharmacologically blocked. Accordingly, the inhibition of the TASK-like current induced by acute hypoxia (PO2 ∼5 torr) increased from ∼62% in control cells to ∼96% in the CIH cells.

Present results show that acute hypoxic inhibition of TASK-like K+ channel is potentiated by CIH exposure, suggesting that the enhancing effect of CIH on CB chemosensory responsiveness to hypoxia occurs at the initial step of the oxygen transduction in the CB chemoreceptor cells.

Keywords

Carotid body Chemosensory discharge Glomus cells TASK channels Acute hypoxia Single channel recording Intermittent hypoxia Obstructive sleep apnea 

Notes

Acknowledgements

This work was supported by grant 1100405 from the National Fund for Scientific and Technological Development of Chile (FONDECYT).

References

  1. Buckler KJ (1999) Background leak K+-currents and oxygen sensing in carotid body type 1 cells. Respir Physiol 115:179–187CrossRefPubMedGoogle Scholar
  2. Buckler KJ (2010) Two-pore domain K+ channels and their role in chemoreception. Adv Exp Med Biol 66:15–30CrossRefGoogle Scholar
  3. Del Rio R, Moya EA, Iturriaga R (2010) Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link. Eur Resp J 36:143–150CrossRefGoogle Scholar
  4. Garvey JF, Taylor CT, McNicholas WT (2009) Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Resp J 33:1195–1205CrossRefGoogle Scholar
  5. Iturriaga R, Varas R, Alcayaga J (2007) Electrical and pharmacological properties of petrosal ganglion neurons that innervate the carotid body. Resp Physiol Neurobiol 157:130–139CrossRefGoogle Scholar
  6. Iturriaga R, Moya EA, Del Rio R (2009) Carotid body potentiation induced by intermittent hypoxia: implications for cardiorespiratory changes induced by sleep apnoea. Clin Exp Pharmacol Physiol 36:1197–1204CrossRefPubMedGoogle Scholar
  7. Kim D, Cavanaugh EJ, Kim I, Carroll JL (2009) Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells. J Physiol 587:2963–2975CrossRefPubMedGoogle Scholar
  8. Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR (2003) Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci U S A 100:10073–10078CrossRefPubMedGoogle Scholar
  9. Rey S, Del Rio R, Alcayaga J, Iturriaga R (2004) Chronic intermittent hypoxia enhances cat chemosensory and ventilatory responses to hypoxia. J Physiol 560:577–586CrossRefPubMedGoogle Scholar
  10. Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T (2008) Sleep apnea and cardiovascular disease. J Am Coll Cardiol 52:686–717CrossRefPubMedGoogle Scholar
  11. Varas R, Wyatt CN, Buckler KJ (2007) Modulation of TASK-like background potassium channels in rat arterial chemoreceptor cells by intracellular ATP and other nucleotides. J Physiol 583:521–536CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Fernando C. Ortiz
    • 1
  • Rodrigo Del Rio
    • 1
  • Rodrigo Varas
    • 1
  • Rodrigo Iturriaga
    • 1
    Email author
  1. 1.Laboratorio de Neurobiología, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile

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