Submitted on October 31, 2007
Accepted on April 22, 2008
Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolic flight
Satoshi Okumura1, Takashi Tsunematsu1, Yunzhe Bai1, Qibin Jiao1, Shinji Ono1, Sayaka Suzuki1, Reiko Kurotani1, Motohiko Sato1, Susumu Minamisawa1, Satoshi Umemura2, and Yoshihiro Ishikawa1*
1 Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
2 Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
* To whom correspondence should be addressed. E-mail: yishikaw{at}med.yokohama-cu.ac.jp.
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 
-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 tencency 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. Putting together, AC5 plays a major role in stabilizing heat rate under microgravity.
