Journal of Applied Physiology AJP: Gastrointestinal and Liver Physiology
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J Appl Physiol 96: 1187-1195, 2004; doi:10.1152/japplphysiol.00929.2003
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INVITED REVIEW

HIGHLIGHTED TOPICS
Oxygen Sensing in Health and Disease

Regulation of oxygen sensing by ion channels

José López-Barneo, Raquel del Toro, Konstantin L. Levitsky, María D. Chiara, and Patricia Ortega-Sáenz

Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, E-41013 Seville, Spain

O2 sensing is of critical importance for cell survival and adaptation of living organisms to changing environments or physiological conditions. O2-sensitive ion channels are major effectors of the cellular responses to hypoxia. These channels are preferentially found in excitable neurosecretory cells (glomus cells of the carotid body, cells in the neuroepithelial bodies of the lung, and neonatal adrenal chromaffin cells), which mediate fast cardiorespiratory adjustments to hypoxia. O2-sensitive channels are also expressed in the pulmonary and systemic arterial smooth muscle cells where they participate in the vasomotor responses to low O2 tension (particularly in hypoxic pulmonary vasoconstriction). The mechanisms underlying O2 sensing and how the O2 sensors interact with the ion channels remain unknown. Recent advances in the field give different support to the various current hypotheses. Besides the participation of ion channels in acute O2 sensing, they also contribute to the gene program developed under chronic hypoxia. Gene expression of T-type calcium channels is upregulated by hypoxia through the same hypoxiainducible factor-dependent signaling pathway utilized by the classical O2-regulated genes. Alteration of acute or chronic O2 sensing by ion channels could participate in the pathophysiology of human diseases, such as sudden infant death syndrome or primary pulmonary hypertension.

Electrophysiology; Gene Expression; Hypoxia-Inducible Factors


Address for reprint requests and other correspondence: J. López-Barneo, Laboratorio de Investigaciones Biomédicas, Edificio de Laboratorios, 2a planta, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, E-41013 Sevilla, Spain (E-mail: Jose.L.Barneo.sspa{at}juntadeandalucia.es).




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