Type 5 adenylyl cyclase plays a major role in regulating autonomic response to microgravity in the heart

Abstract

Objective: Autonomic nervous activity is altered under microgravity. Cardiac response to autonomic regulation is mostly determined by β-adrenergic receptors/cAMP signal that is regulated by adenylyl cyclase (AC). We thus examined the role of a major cardiac AC isoform, type 5 AC (AC5), in the autonomic regulation of the heart under microgravity induced by parabolic flights. Methods: We used transgenic mice with either disrupted (AC5KO) or overexpressed AC5 in the heart (AC5TG), and analyzed heart rate variability during parabolic flight. Results: The standard deviation of normal R-R intervals, a marker of total autonomic variability, was significantly greater under microgravity in AC5KO while no significant changes in WT and AC5TG. LF (low frequency)/HF (high frequency), a marker of sympathetic activity, became significantly lower under microgravity in WT and AC5TG while there was no such a decrease in AC5KO. Normalized HF, a marker of parasympathetic activity, became significantly greater in WT under microgravity, and became even greater in AC5TG, while no such increase in AC5KO. Conclusions: Putting together, changes in autonomic indexes in response to microgravity were augmented in AC5TG while attenuated in AC5KO, suggesting that AC5 plays a major role in determining the magnitude of cardiac responses to autonomic regulation under microgravity. [J Physiol Sci. 2008;58 Suppl:S180]