TY - JOUR
T1 - Modified autonomic regulation in mice mutated in the β4 subunit of the lh/lh calcium channel
AU - Murakami, Manabu
AU - Suzuki, Takashi
AU - Wu, Tsai Wen
AU - Kuwasako, Kenji
AU - Takahashi, Eiki
AU - Watanabe, Hiroyuki
AU - Murakami, Agnieszka M.
AU - Miyoshi, Ichiro
AU - Yanagisawa, Teruyuki
AU - Sasano, Hironobu
AU - Ono, Kyoichi
AU - Ohba, Takayoshi
N1 - Funding Information:
This research was sponsored in part by Grants-in-Aid for Scientific Research from JSPS, KAKENHI ( 25460293 ), The Center of Healthy Aging Innovation (COI), the Special Project of Three Northern Tohoku Universities, and a program titled “Influence of socio-environmental factors on the progression of atherosclerosis among the general population.” Appendix A
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/5/8
Y1 - 2015/5/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2015.03.112
DO - 10.1016/j.bbrc.2015.03.112
M3 - Article
C2 - 25892515
AN - SCOPUS:84937765363
VL - 461
SP - 200
EP - 205
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -