Basic Mechanisms of Oxygen Sensing and Adaptation to Hypoxia

Introduction

A large body of experimental work has been performed on oxygen sensing and on the cellular events that result from oxygen deprivation in a variety of cell types and organisms. Such comparative studies have contributed to our understanding of O ₂ sensing and adaptation to hypoxia. As a result, a number of new concepts and mechanisms regarding O ₂ sensing and hypoxia adaptation have emerged. It has been shown that neurons, renal and respiratory epithelial cells, hepatocytes, myocardial cells, vascular smooth muscle, or endothelial cells—virtually every cell type studied—can sense O ₂ , one way or another. This type of investigation has also been done at various ages, and age has been very important in determining sensing, responsiveness, and the ability to adapt to lack of O ₂ . Because in the past we have generally focused our study on nerve and glial cells during O ₂ deprivation, this chapter summarizes mostly the studies on excitable tissues. However, an extensive body of new knowledge has demonstrated that much of what is known about the heart’s sensing mechanisms can be applied to the central nervous system, for example, and much of what we know about the renal epithelium can be applied to the respiratory cells. It should be recognized that although there are similarities among tissues, there are often major differences. These differences reflect either differing environments or the function of that particular cell type of tissue. In certain instances, when the duration and severity of the stimulus are not too overwhelming, nerve cells may adapt and possibly survive hypoxia. Often, however, when the stress is too severe, the response time of the cells, from sensing to actual injury, is considerably shortened, and it is often difficult to tease apart the processes that control the various stages of response.

The aim of this chapter is to highlight observations that will demonstrate that a number of potential O ₂ sensors exist in nerve cells. We detail results and data regarding ionic flux and controlling ionic flux mechanisms. We also detail some newer observations regarding expressional regulation of genes and adaptation to O ₂ deprivation that occurs over much longer periods of time.