title: Modified sympathetic nerve regulation in AKAP5-null mice.
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.
authors.affiliation: Department of Pharmacology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Chong
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Department of Cellular Physiology, Akita University, Graduate School of Medicine, 1-1-1 Hondoh, Akita, 010-8543, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohba
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Nishizaki
authors.affiliation: Department of Pharmacology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ogata
authors.affiliation: Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
authors.affiliation: Department of Molecular Pharmacology, Tohoku University School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Yanagisawa
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osanai
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.affiliation: Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsubara
authors.affiliation: Department of Cellular Physiology, Akita University, Graduate School of Medicine, 1-1-1 Hondoh, Akita, 010-8543, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Cellular Physiology, Akita University, Graduate School of Medicine, 1-1-1 Hondoh, Akita, 010-8543, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Department of Pharmacology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. Electronic address: mmura0123@hotmail.co.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology*; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D054758:A Kinase Anchor Proteins; C520665:Akap5 protein, mouse
keywords: Heart rate; Mouse; PKA; Parasympathetic nerve; Sympathetic nerve