Regulation of Ionic Conductances and Gene Expression by Hypoxia in an Oxygen Sensitive Cell Line

Abstract

Oxygen is the final acceptor of electrons in the synthesis of ATP by the mitochondrial respiratory chain and is therefore an obligatory substrate for energy transformation in most biological systems. A reduction in O₂ tension severely limits the ability of cells to perform energy-dependent functions and, if the hypoxia is severe enough, it can be life threatening. It is therefore not surprising that an elaborate control system has evolved in most species for optimizing the delivery of O₂ to cells. In mammals, an essential component of this system is the carotid body; a small organ that is located bilaterally at the bifurcation of the carotid artery. The carotid body contains O₂-sensitive (type I) cells that are stimulated by reduced O₂ tension. The type I cells transmit information concerning the O₂ status of arterial blood to closely situated primary sensory afferent fibers by release of neurotransmitter. A major problem confronting contemporary biology is identification of the molecular and cellular mechanisms that couple environmental stimuli with changes in cell phenotype and function. However, after several decades of intense investigations, the mechanisms by which type I cells detect changes in O₂ tension and transduce this signal into an increase in neurotransmitter synthesis and release remain unknown.