Comparative mechanisms of O2 and CO2/H+ chemoreception in vertebrates

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Multicellular organisms display a variety of sensory receptors, which allow them to sense variations in environmental stimuli, and make appropriate responses crucial for survival. Since oxygen (O2) is essential for the survival of many organisms, specialized O2-receptors help maintain an optimal supply of oxygen to the body tissues so as to meet the metabolic needs of individual cells. Some of these O2-receptors are able to detect CO2/H+ as well. The cellular/molecular mechanisms of O2 and CO2/H+ sensing are not well understood. My laboratory is interested in understanding these mechanisms, as well as their evolution in vertebrates. Much of our work to date has focused on air-breathing mammals, where particular chemoreceptive organs (e.g. carotid body and adrenal gland) contain cells endowed with specialized mechanisms for detecting low O2 (hypoxia) and elevated CO2/H+. The basic mechanisms probably arose first in water-breathing animals, e.g. fish, and with the aid of NSERC support over the last several years my laboratory carried out an important series of pioneering studies on the mechanisms of O2 sensing and innervation patterns in the zebrafish gill model. We studied how specific ion channel proteins in these receptors (i.e. neuroepithelial cells or NECs) are modified by low O2, and how nerve fibers project to these cells in several aquatic vertebrates. In this renewal application we will extend our comparative analysis to include NECs of the amphibian (Xenopus) gill. Our working hypothesis is that the fundamental mechanisms of O2 and CO2/H+ sensing, that have been studied extensively in mammals, arose first in water-breathers and are conserved among the vertebrates. We will test the idea that regulation of K+ channel activity is a highly conserved mechanism in these sensing pathways and that the recently-proposed gaseous signaling molecule, i.e. hydrogen sulfide (H2S), may play a more general role in hypoxia-sensing. This important research is expected to yield insight into how animals (including humans) sense and adapt to low O2 and high CO2/H+ conditions, and why failure to do so leads to life-threatening situations.