Ph.D., State University of New York at Buffalo, Roswell Park Division, 1995
Circadian rhythms are approximate 24-hour biological cycles that synchronize the timing of an organism's behavior and physiology to daily environmental changes. This temporal coordination has been experimentally shown to provide an adaptive advantage by enhancing an organism's ability to respond to daily changes in light, temperature, and humidity. The importance of these rhythms to human health is highlighted by epidemiological studies of shift workers, who often display circadian disturbances, showing they have a range of health problems including increased occurrence of cardiovascular disease. In addition, the incidence of cardiovascular events such as acute myocardial infarction, sudden death, and arrhythmia exhibits a striking time of day dependence with events peaking between 6 AM and noon. Circadian osscillations in heart rate, blood pressure, and cardiac output have been traditionally attributed to daily rhythms of sympathetic activity, catecholamines and hormones, under the control of the suprachiasmatic nucleus. However, recent literature, including our own, suggests a role for peripheral circadian clocks, and in particular, the heart molecular clock, as modulators of these parameters. Current data from our lab has identified several ion channels, including Scn5a as genes expressed in a circadian manner, raising an intriguing new mechanism whereby environmental or lifestyle factors which disrupt the molecular clock can contribute to altered ion channel expression. Understanding the link between the molecular clock and the regulation of ion channel expression in the heart is of critical importance to fully grasp how normal cardiac rhythm is maintained.