Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolic flight.
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 beta-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.
Okumura
Satoshi
S
Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Tsunematsu
Takashi
T
Bai
Yunzhe
Y
Jiao
Qibin
Q
Ono
Shinji
S
Suzuki
Sayaka
S
Kurotani
Reiko
R
Sato
Motohiko
M
Minamisawa
Susumu
S
Umemura
Satoshi
S
Ishikawa
Yoshihiro
Y
D000262:Adenylyl Cyclases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D015153:Blotting, Western; D004562:Electrocardiography; D006321:Heart / Q000502:physiology; D006339:Heart Rate / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018474:Weightlessness Simulation / Q000009:adverse effects*
D007527:Isoenzymes; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V