title: Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels.
abstract: N-type voltage-dependent Ca(2+) 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 alpha(1B) subunit (Ca(v) 2.2). The alpha(1B)-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 omega-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.
authors: Tsukuba Research Laboratories, Eisai Co., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.
authors: M
authors: M
authors: Ino
authors: T
authors: T
authors: Yoshinaga
authors: M
authors: M
authors: Wakamori
authors: N
authors: N
authors: Miyamoto
authors: E
authors: E
authors: Takahashi
authors: J
authors: J
authors: Sonoda
authors: T
authors: T
authors: Kagaya
authors: T
authors: T
authors: Oki
authors: T
authors: T
authors: Nagasu
authors: Y
authors: Y
authors: Nishizawa
authors: I
authors: I
authors: Tanaka
authors: K
authors: K
authors: Imoto
authors: S
authors: S
authors: Aizawa
authors: S
authors: S
authors: Koch
authors: A
authors: A
authors: Schwartz
authors: T
authors: T
authors: Niidome
authors: K
authors: K
authors: Sawada
authors: Y
authors: Y
authors: Mori
mesh_terms: D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002339:Carotid Arteries / Q000503:physiopathology; D004553:Electric Conductivity; D004558:Electric Stimulation; D017353:Gene Deletion; D006325:Heart Atria / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D009200:Myocardial Contraction; D009474:Neurons / Q000378:metabolism; D021122:Protein Subunits; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D020864:Calcium Channels, N-Type; D021122:Protein Subunits; D020866:omega-Conotoxin GVIA; D002118:Calcium