Modified autonomic regulation in mice mutated in the β4 subunit of the lh/lh calcium channel

Manabu Murakami, Takashi Suzuki, Tsai Wen Wu, Kenji Kuwasako, Eiki Takahashi, Hiroyuki Watanabe, Agnieszka M. Murakami, Ichiro Miyoshi, Teruyuki Yanagisawa, Hironobu Sasano, Kyoichi Ono, Takayoshi Ohba

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)200-205
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2015 May 8


  • Calcium channel
  • Heart rate
  • Mouse
  • Parasympathetic nerve
  • Sympathetic nerve


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