Regulation of oxygen sensing by ion channels

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 hypoxia-inducible 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.