Modified sympathetic regulation in N-type calcium channel null-mouse.
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.
Murakami
Manabu
M
Department of Pharmacology, Akita University School of Medicine, Akita, Japan. mmura0123@hotmail.co.jp
Ohba
Takayoshi
T
Wu
Tsai-Wen
TW
Fujisawa
Susumu
S
Suzuki
Takashi
T
Takahashi
Yoichiro
Y
Takahashi
Eiki
E
Watanabe
Hiroyuki
H
Miyoshi
Ichiro
I
Ono
Kyoichi
K
Sasano
Hironobu
H
Ito
Hiroshi
H
Iijima
Toshihiko
T
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
D020864:Calcium Channels, N-Type; D020908:Calcium Channels, R-Type