Ca2+ channel α1B subunit (CaV 2.2) knockout mouse reveals a predominant role of N-type channels in the sympathetic regulation of the circulatory system

Yasuo Mori, Motohiro Nishida, Shunichi Shimizu, Masakazu Ishii, Takashi Yoshinaga, Mitsuhiro Ino, Kohei Sawada, Tetsuhiro Niidome

Research output: Contribution to journalReview article

32 Citations (Scopus)

Abstract

N-type voltage-dependent Ca2+ channels (VDCCs), predominantly localized in the nervous system, have been proposed to play vital roles in a variety of neuronal functions such as neurotransmitter release at sympathetic nerve terminals. To directly approach the elucidation of the physiological significance of N-type VDCCs in the autonomic nervous system, α1B subunit (CaV 2.2)-deficient mice were generated, in which peripheral neurons showed a complete and selective elimination of N-type channel currents sensitive to ω-conotoxin GVIA (the peptide toxin from the fish-hunting cone snail Conus geographus), without a significant effect on the activity of other VDCC types. In isolated left atria prepared from N-type-deficient mice, the positive inotropic response mediated by the sympathetic nervous system was dramatically decreased, whereas the negative inotropic response mediated by parasympathetic neurons was nearly intact compared with those of normal mice. The baroreflex response to bilateral carotid occlusion was markedly reduced in the mutant mice. Interestingly, the mutant mice showed sustained elevation of heart rate and blood pressure. These results provide direct in vivo evidence for an essential role of N-type VDCCs in maintaining the normal function of the sympathetic nervous system in circulatory regulation, demonstrating a potential of N-type VDCC-deficient mice as a useful model for studying disorders attributable to sympathetic nerve dysfunction.

Original languageEnglish
Pages (from-to)270-275
Number of pages6
JournalTrends in Cardiovascular Medicine
Volume12
Issue number6
DOIs
Publication statusPublished - Aug 2002
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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