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Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolic flight

¹Cardiovascular Research Institute and ²Department of Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama; ³Department of Life Science and Medical Bio-Science, Waseda University, Tokyo, Japan; and ⁴Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine and Medicine (Cardiology), New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey

Submitted 31 October 2007 ; accepted in final form 22 April 2008

It is well known that autonomic nervous activity is altered under microgravity, leading to disturbed regulation of cardiac function, such as heart rate. Autonomic regulation of the heart is mostly determined by β-adrenergic receptors/cAMP signal, which is produced by adenylyl cyclase, in cardiac myocytes. To examine a hypothesis that a major cardiac isoform, type 5 adenylyl cyclase (AC5), plays an important role in regulating heart rate during parabolic flights, we used transgenic mouse models with either disrupted (AC5KO) or overexpressed AC5 in the heart (AC5TG) and analyzed heart rate variability. Heart rate had a tendency to decrease gradually in later phases within one parabola in each genotype group, but the magnitude of decrease was smaller in AC5KO than that in the other groups. The inverse of heart rate, i.e., the R-R interval, was much more variable in AC5KO and less variable in AC5TG than that in wild-type controls. The standard deviation of normal R-R intervals, a marker of total autonomic variability, was significantly greater in microgravity phase in each genotype group, but the magnitude of increase was much greater in AC5KO than that in the other groups, suggesting that heart rate regulation became unstable in the absence of AC5. In all, AC5 plays a major role in stabilizing heat rate under microgravity.

transgenic mouse; autonomic nerve activity; heart rate variability