RUI: Comparative Hypoxic Chemosensitivity of Two Rat Strains

Eastern Washington University, Cheney WA

Investigators

Abstract

Animals respond to environments that are low in oxygen by increasing their breathing. This increase in breathing is stimulated by oxygen sensitive cells in a structure called the carotid body. There are a number of theories about how the carotid body cells can transduce the signal of low oxygen levels (hypoxia) in the blood into nerve signals to the brain that cause the increase in breathing, but which theory is correct remains unresolved. Oxygen is carried in the blood on hemoglobin that is present in red blood cells. Hemoglobin is a so-called 'heme'-protein and there are other heme-proteins in other cells in the body. One of the theories about how carotid body cells sense changes in oxygen levels is via a heme-protein that can bind oxygen either inside the cell or at its membrane. Comparative studies of several species of mammals, birds and even some reptiles have demonstrated a good correlation between the affinity of hemoglobin for oxygen, or the ease with which hemoglobin binds oxygen, and the amount of decline in oxygen in the blood required to stimulate an increase in breathing. The mechanism underlying this observation may be a matching or commonality of oxygen binding characteristics of the b-type heme protein binding oxygen in the blood and a b-type heme protein binding oxygen in the oxygen sensitive cells of the carotid bodies. If this is the case, the mechanism may help elucidate not only how the carotid bodies work but how the control of breathing has evolved to be well matched to the oxygen transport properties of the blood. To explore this concept further this project will investigate two strains of rats that exhibit different breathing and metabolic responses to reduced oxygen or hypoxia. The binding characteristics of their hemoglobin will be determined to see if they differ, and the response characteristics, or sensitivity, of their carotid bodies to hypoxia will be measured to determine whether or not the differences in hypoxic sensitivity of the whole animal, in terms of breathing and metabolism, can be related to differences in the hypoxic sensitivity of the carotid body. If they are related, then future comparative studies of heme-proteins in the carotid bodies and oxygen sensitive ion channels will be conducted. If not, then alternative hypotheses about the mechanisms controlling the different hypoxic sensitivities will be pursued.