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Voltage-dependent calcium channel β subunit-derived peptides reduce excitatory neurotransmission and arterial blood pressure

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Author(s)
Haein Weon Jiyeon Jun Tae Wan Kim Kibeom Park Hyung Kyu Kim Dong-Ho Youn
Keimyung Author(s)
Park, Ki Bum
Department
Dept. of Anesthesiology & Pain Medicine (마취통증의학)
Journal Title
Life sciences
Issued Date
2021
Volume
264
Keyword
Voltage-dependent calcium channelβsubunitSubunit interactionCa2+ currentExcitatory postsynaptic currentArterial blood pressure
Abstract
Aims:
Voltage-dependent calcium channels (VDCCs) play an important role in various physiological functions in the nervous system and the cardiovascular system. In L-, N-, P/Q-, and R-type VDCCs, β subunit assists the channels for membrane targeting and modulates channel properties. In this study, we investigated whether an inhibition of the β subunit binding to α subunit, the pore-forming main subunit of VDCCs, have any effect on channel activation and physiological functions.

Main methods:
Peptides derived from the specific regions of β subunit that bind to the α-interaction domain in I-II linker of α subunit were manufactured, presuming that the peptides interrupt α-β subunit interaction in the channel complex. Then, they were tested on voltage-activated Ca2+ currents recorded in acutely isolated trigeminal ganglion (TG) neurons, excitatory postsynaptic currents (EPSCs) in the spinal dorsal horn neurons, and arterial blood pressure (BP) recorded from the rat femoral artery.

Key findings:
When applied internally through patch pipettes, the peptides decreased the peak amplitudes of the voltage-activated Ca2+ currents. After fusing with HIV transactivator of transcription (TAT) sequence to penetrate cell membrane, the peptides significantly decreased the peak amplitudes of Ca2+ currents and the peak amplitudes of EPSCs upon the external application through bath solution. Furthermore, the TAT-fused peptides dose dependently reduced the rat BP when administered intravenously.

Significance:
These data suggest that an interruption of α-β subunit association in VDCC complex inhibits channel activation, thereby reducing VDCC-mediated physiological functions such as excitatory neurotransmission and arterial BP.
Keimyung Author(s)(Kor)
박기범
Publisher
School of Medicine (의과대학)
Citation
Haein Weon et al. (2021). Voltage-dependent calcium channel β subunit-derived peptides reduce excitatory neurotransmission and arterial blood pressure. Life sciences, 264, 118690. doi: 10.1016/j.lfs.2020.118690
Type
Article
ISSN
1879-0631
Source
https://www.sciencedirect.com/science/article/abs/pii/S0024320520314430
DOI
10.1016/j.lfs.2020.118690
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43234
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Anesthesiology & Pain Medicine (마취통증의학)
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