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Modified sympathetic nerve regulation in AKAP5-null mice.

Authors :: Han C
Tomita H
Ohba T
Nishizaki K
Ogata Y
Matsuzaki Y
Sawamura D
Yanagisawa T
Osanai T
Imaizumi T
Matsubara A
Adachi T
Ono K
Okumura K
Murakami M
Source :: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2016 Jan 22; Vol. 469 (4), pp. 897-902. Date of Electronic Publication: 2015 Dec 20.
Publication Year :: 2016
Abstract: Genetic analyses have revealed an important association between A-kinase anchoring proteins (AKAPs) and the intracellular calcium modulating system. AKAP5, also known as AKAP79/150, is an anchoring protein between PKA and voltage-dependent calcium channels, ryanodine receptor-2, phospholamban and other molecules. The aim of the present study was to elucidate the physiological importance of AKAP5 in the creation of cardiac rhythm using AKAP5-null mice. ECG analysis showed a normal sinus rhythm and a decreased responsiveness to isoproterenol in AKAP5-null mice compared with wild-type mice. Analysis of heart rate variability revealed that the R-R interval was unstable in AKAP5-null mutants and that the low-frequency components had decreased, indicating that the tonus of the sympathetic nervous system was affected. Furthermore, the atrium of the AKAP5-null mice showed a decreased positive inotropic response to isoproterenol, indicating the involvement of AKAP5 in a PKA-dependent pathway. Thus, our present study revealed that AKAP5 plays a significant role in the regulation of sympathetic nerve activities.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)