title: Modified autonomic regulation in mice mutated in the β4 subunit of the lh/lh calcium channel.
abstract: Genetic analyses have revealed an important association between P/Q-type calcium channel activities and hereditary neurological disorders. The P/Q-type channels are composed principally of heterologous multimeric subunits including CaV2.1 and CaVβ4. Of these, the β4 subunit is thought to play a significant role in channel physiology, because a mouse line mutant in that subunit (the lethargic mouse: lh) exhibits a severe ataxic phenotype. The aim of the present study was to elucidate the physiological importance of the β4 subunit. ECG analysis showed that the T wave was high in 8-week-old lh mutants; this may be associated with hyperkalemia. Upon pharmacological ECG analysis, 2-3-week-old lh mutants exhibited reduced responses to a β-blocker and a muscarinic receptor antagonist. Analysis of heart rate variability revealed that the R-R interval was unstable in lh mutants and that both the low- and high-frequency components had increased in extent, indicating that the tonus of both the sympathetic and parasympathetic nervous systems was modified. Thus, our present study revealed that the β4 subunit played a significant role in regulation of sympathetic and parasympathetic nerve activities.
authors.affiliation: Department of Pharmacology, Hirosaki University, Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: mmura0123@hotmail.co.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Cellular Physiology, Akita University, Graduate School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan.
authors.forename: Tsai-Wen
authors.initials: TW
authors.lastname: Wu
authors.affiliation: Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwasako
authors.affiliation: Support Unit for Animal Experiments, Riken Brain Science Institute, RIKEN, Brain Science Institute, Research Resources Center Support Unit for Animal Experiments, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Akita University, Graduate School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacology, Hirosaki University, Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Murakami
authors.affiliation: Center for Experimental Animal Science, Tohoku University School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.affiliation: Department of Molecular Pharmacology, Tohoku University School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Yanagisawa
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of Cellular Physiology, Akita University, Graduate School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Cellular Physiology, Akita University, Graduate School of Medicine, 1-1-1 Hondoh, Akita 010-8543, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohba
mesh_terms: D000818:Animals; D001483:Base Sequence; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D006339:Heart Rate; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010275:Parasympathetic Nervous System / Q000502:physiology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D020864:Calcium Channels, N-Type; D021122:Protein Subunits
keywords: Calcium channel; Heart rate; Mouse; Parasympathetic nerve; Sympathetic nerve