The vast majority of vertebrate species are unable to survive without access to oxygen. Death quickly ensues from oxygen lack due to the failure of organs, such as the heart, which require a constant supply of oxygen to create the metabolic energy necessary to support their continued function. However, in stark contrast to "normal" vertebrates, a few vertebrate species have evolved the remarkable ability to survive for prolonged periods in the complete absence of oxygen (termed anoxia). This research focuses on elucidating how the heart of one of the vertebrate champions of anoxia survival, the red-eared slider turtle (Trachemys scripta), can continue to beat rhythmically during anoxia, albeit more slowly. Previous research has revealed that the intrinsic rate at which the turtle heart beats is vastly slowed by anoxia exposure. However, the mechanisms that act to suppress the intrinsic heart rate during anoxia remain unknown. In the vertebrate heart, intrinsic heart rate is determined by cells located in a specialized region, termed the cardiac pacemaker. The pacemaker cells initiate cardiac contraction by producing electrical impulses, called pacemaker action potentials, the rate of which sets intrinsic heart rate. This research will utilize a multi-tiered and multidisciplinary approach to investigate the physiological mechanisms by which anoxia and low temperature modulates pacemaker rate. Ultimately, by probing how a vertebrate heart can continue to beat in the absence of oxygen, this research will develop a deeper understanding of the connections between oxygen, metabolism and electrical excitation, which are a crucial aspect of basic cardiac biology. In addition, the intimate intertwining of research activities with training, education and mentoring opportunities in contemporary physiology and cell biology for students at UAA as well as those of the broader Alaskan community will broaden exposure and enhance opportunity in scientific research for individuals that are underrepresented in STEM disciplines.
Remarkably, the heart of one of the vertebrate champions of anoxia survival, the red-eared slider turtle (Trachemys scripta) can continue to beat rhythmically during anoxia, albeit more slowly. Previous research has revealed that a dramatic and rapid resetting of the intrinsic pacemaker contributes to the bradycardia displayed by the anoxic turtle. However, the mechanism by which anoxia modulates pacemaker rate remains unknown. The overarching objective of this research is to exploit the turtle heart as a model to elucidate the physiological and cellular mechanisms of cardiac pacemaker regulation. This research will utilize a multi-tiered and multidisciplinary approach to systematically investigate in the organ (contractile properties of isolated heart chambers; in vitro recordings of pacemaker action potentials) and cell (electrophysiological measures of ionic currents in isolated cardiomyocytes) the alterations of the cardiac pacemaker that underlies the resetting of intrinsic heart rate by anoxia. The proposed research will provide important insights into the molecular mechanisms of cardiac pacemaking in conditions of low oxygen and temperature. Both have pertinence to basic cardiac biology as well as human pathology, and the anoxic turtle provides a remarkable model of how these processes persist in conditions of substantial stress.
