Functional disorders of the sympathetic nervous system in mice lacking the α1B subunit (Cav 2.2) of N-type calcium channels

Mitsuhiro Ino, Takashi Yoshinaga, Minoru Wakamori, Norimasa Miyamoto, Eiki Takahashi, Jiro Sonoda, Takaki Kagaya, Tohru Oki, Takeshi Nagasu, Yukio Nishizawa, Isao Tanaka, Keiji Imoto, Shinichi Aizawa, Sheryl Koch, Arnold Schwartz, Tetsuhiro Niidome, Kohei Sawada, Yasuo Mori

研究成果: Article査読

113 被引用数 (Scopus)

抄録

N-type voltage-dependent Ca2+ channels (VDCCs), predominantly localized in the nervous system, have been considered to play an essential role in a variety of neuronal functions, including neurotransmitter release at sympathetic nerve terminals. As a direct approach to elucidating the physiological significance of N-type VDCCs, we have generated mice genetically deficient in the α1B subunit (Cav 2.2). The α1B-deficient null mice, surprisingly, have a normal life span and are free from apparent behavioral defects. A complete and selective elimination of N-type currents, sensitive to ω-conotoxin GVIA, was observed without significant changes in the activity of other VDCC types in neuronal preparations of mutant mice. The baroreflex response, mediated by the sympathetic nervous system, was markedly reduced after bilateral carotid occlusion. In isolated left atria prepared from N-type-deficient mice, the positive inotropic responses to electrical sympathetic neuronal stimulation were dramatically decreased compared with those of normal mice. In contrast, parasympathetic nervous activity in the mutant mice was nearly identical to that of wild-type mice. Interestingly, the mutant mice showed sustained elevation of heart rate and blood pressure. These results provide direct evidence that N-type VDCCs are indispensable for the function of the sympathetic nervous system in circulatory regulation and indicate that N-type VDCC-deficient mice will be a useful model for studying disorders attributable to sympathetic nerve dysfunction.

本文言語English
ページ(範囲)5323-5328
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
98
9
DOI
出版ステータスPublished - 2001 4 24
外部発表はい

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