Modified autonomic regulation in mice mutated in the β4 subunit of the lh/lh calcium channel
| Autor: | Teruyuki Yanagisawa, Hironobu Sasano, Agnieszka M. Murakami, Kenji Kuwasako, Hiroyuki Watanabe, Manabu Murakami, Takayoshi Ohba, Kyoichi Ono, Eiki Takahashi, Takashi Suzuki, Ichiro Miyoshi, Tsai Wen Wu |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Sympathetic Nervous System Genotype Protein subunit Mutant Molecular Sequence Data Biophysics Heterologous Biology Biochemistry Mice Calcium Channels N-Type Heart Rate Parasympathetic Nervous System Internal medicine Heart rate Muscarinic acetylcholine receptor medicine Animals Molecular Biology Base Sequence Calcium channel Antagonist Heart Cell Biology Phenotype Protein Subunits Endocrinology Mutation |
| Zdroj: | Biochemical and biophysical research communications. 461(2) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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