Regulation of oxygen sensing by ion channels

Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, E-41013 Seville, Spain O 2 sensing is of critical importance for cell survival and adaptation of living organisms to changing environments or physiological conditions. O 2 -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. O 2 -sensitive channels are also expressed in the pulmonary and systemic arterial smooth muscle cells where they participate in the vasomotor responses to low O 2 tension (particularly in hypoxic pulmonary vasoconstriction). The mechanisms underlying O 2 sensing and how the O 2 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 O 2 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 O 2 -regulated genes. Alteration of acute or chronic O 2 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, 2 a planta, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, E-41013 Sevilla, Spain (E-mail: Jose.L.Barneo.sspa{at}juntadeandalucia.es ).