Modified sympathetic nerve regulation in AKAP5-null mice

作者:Han Chong; Tomita Hirofumi; Ohba Takayoshi; Nishizaki Kimitaka; Ogata Yoshiki; Matsuzaki Yasushi; Sawamura Daisuke; Yanagisawa Teruyuki; Osanai Tomohiro; Imaizumi Tadaatsu; Matsubara Atsushi; Adachi Takeshi; Ono Kyoichi; Okumura Ken; Murakami Manabu*
来源:Biochemical and Biophysical Research Communications, 2016, 469(4): 897-902.
DOI:10.1016/j.bbrc.2015.12.057

摘要

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.

  • 出版日期2016-1-22