title: Modified sympathetic regulation in N-type calcium channel null-mouse.
abstract: To elucidate the physiological importance of neuronal (N)-type calcium channels in sympathetic controls, we analyzed N-type channel-deficient (NKO) mice. Immunoprecipitation analysis revealed increased interaction between beta3 (a major accessory subunit of N-type channels) and R-type channel-forming CaV2.3 in NKO mice. R-R intervals in NKO ECG recordings were elongated and fluctuating, suggesting disturbed sympathetic tonus. N-type channel inhibitors elongated the R-R interval in control mice, whereas R-type channel blocking with SNX-482 significantly affected NKO but not control mice, indicating a compensatory role for R-type channels. Echocardiography and Langendorff heart analysis confirmed a major role for R-type channels in NKO mice. Combined, our biochemical and physiological analyses strongly suggest that the remaining sympathetic tonus in NKO mice is dependent on R-type calcium channels.
authors.affiliation: Department of Pharmacology, Akita University School of Medicine, Akita, Japan. mmura0123@hotmail.co.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohba
authors.forename: Tsai-Wen
authors.initials: TW
authors.lastname: Wu
authors.forename: Susumu
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iijima
mesh_terms: D000311:Adrenal Glands / Q000648:ultrastructure; D000818:Animals; D020864:Calcium Channels, N-Type / Q000172:deficiency / Q000502:physiology*; D020908:Calcium Channels, R-Type / Q000502:physiology; D004452:Echocardiography; D006321:Heart / Q000294:innervation; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D010477:Perfusion; D013564:Sympathetic Nervous System / Q000502:physiology*; D016276:Ventricular Function
chemical_list: D020864:Calcium Channels, N-Type; D020908:Calcium Channels, R-Type