PMID- 30744067
OWN - NLM
STAT- MEDLINE
DCOM- 20190529
LR  - 20200225
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 3
DP  - 2019 Feb 8
TI  - BmK AEP, an Anti-Epileptic Peptide Distinctly Affects the Gating of Brain 
      Subtypes of Voltage-Gated Sodium Channels.
LID - 10.3390/ijms20030729 [doi]
LID - 729
AB  - BmK AEP, a scorpion peptide purified form the venom of Buthus martensii Karsch, 
      has been reported to display anti-epileptic activity. Voltage-gated sodium 
      channels (VGSCs) are responsible for the rising phase of action potentials (APs) 
      in neurons and, therefore, controlling neuronal excitability. To elucidate the 
      potential molecular mechanisms responsible for its anti-epileptic activity, we 
      examined the influence of BmK AEP on AP firing in cortical neurons and how BmK 
      AEP influences brain subtypes of VGSCs (Na(v)1.1(-)1.3 and Na(v)1.6). BmK AEP 
      concentration-dependently suppresses neuronal excitability (AP firing) in primary 
      cultured cortical neurons. Consistent with its inhibitory effect on AP 
      generation, BmK AEP inhibits Na(+) peak current in cortical neurons with an IC(50) 
      value of 2.12 microM by shifting the half-maximal voltage of activation of VGSC to 
      hyperpolarized direction by ~7.83 mV without affecting the steady-state 
      inactivation. Similar to its action on Na(+) currents in cortical neurons, BmK AEP 
      concentration-dependently suppresses the Na(+) currents of Na(v)1.1, Na(v)1.3, and 
      Na(v)1.6, which were heterologously expressed in HEK-293 cells, with IC(50) 
      values of 3.20, 1.46, and 0.39 microM with maximum inhibition of 82%, 56%, and 93%, 
      respectively. BmK AEP shifts the voltage-dependent activation in the 
      hyperpolarized direction by ~15.60 mV, ~9.97 mV, and ~6.73 mV in Na(v)1.1, 
      Na(v)1.3, and Na(v)1.6, respectively, with minimal effect on steady-state 
      inactivation. In contrast, BmK AEP minimally suppresses Na(v)1.2 currents (~15%) 
      but delays the inactivation of the channel with an IC(50) value of 1.69 microM. 
      Considered together, these data demonstrate that BmK AEP is a relatively 
      selective Na(v)1.6 gating modifier which distinctly affects the gating of brain 
      subtypes of VGSCs.
FAU - Zhang, Fan
AU  - Zhang F
AD  - State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory 
      for TCM Evaluation and Translational Development, School of Traditional Chinese 
      Pharmacy, China Pharmaceutical University, Nanjing 211198, China. 
      zhangfan20111112@126.com.
FAU - Wu, Ying
AU  - Wu Y
AD  - State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory 
      for TCM Evaluation and Translational Development, School of Traditional Chinese 
      Pharmacy, China Pharmaceutical University, Nanjing 211198, China. 
      wingwycpu@126.com.
FAU - Zou, Xiaohan
AU  - Zou X
AD  - State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory 
      for TCM Evaluation and Translational Development, School of Traditional Chinese 
      Pharmacy, China Pharmaceutical University, Nanjing 211198, China. 
      imzouxiaohan@163.com.
FAU - Tang, Qinglian
AU  - Tang Q
AD  - State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory 
      for TCM Evaluation and Translational Development, School of Traditional Chinese 
      Pharmacy, China Pharmaceutical University, Nanjing 211198, China. 
      cputangqinglian@163.com.
FAU - Zhao, Fang
AU  - Zhao F
AD  - State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory 
      for TCM Evaluation and Translational Development, School of Traditional Chinese 
      Pharmacy, China Pharmaceutical University, Nanjing 211198, China. 
      zhaofang180930@163.com.
FAU - Cao, Zhengyu
AU  - Cao Z
AUID- ORCID: 0000-0002-2692-2949
AD  - State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory 
      for TCM Evaluation and Translational Development, School of Traditional Chinese 
      Pharmacy, China Pharmaceutical University, Nanjing 211198, China. 
      zycao1999@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20190208
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anticonvulsants)
RN  - 0 (Peptides)
RN  - 0 (Voltage-Gated Sodium Channels)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Anticonvulsants/chemistry/isolation & purification/*pharmacology
MH  - Brain/*drug effects/*metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Gene Expression
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Ion Channel Gating/*drug effects
MH  - Mice
MH  - Neurons/drug effects/metabolism
MH  - Peptides/chemistry/isolation & purification/*pharmacology
MH  - Voltage-Gated Sodium Channels/genetics/*metabolism
PMC - PMC6387193
OTO - NOTNLM
OT  - BmK AEP
OT  - action potentials
OT  - anti-epilepsy
OT  - voltage-gated sodium channels
COIS- The authors declare no conflict of interest.
EDAT- 2019/02/13 06:00
MHDA- 2019/05/30 06:00
PMCR- 2019/02/01
CRDT- 2019/02/13 06:00
PHST- 2018/12/25 00:00 [received]
PHST- 2019/01/26 00:00 [revised]
PHST- 2019/01/31 00:00 [accepted]
PHST- 2019/02/13 06:00 [entrez]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2019/05/30 06:00 [medline]
PHST- 2019/02/01 00:00 [pmc-release]
AID - ijms20030729 [pii]
AID - ijms-20-00729 [pii]
AID - 10.3390/ijms20030729 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Feb 8;20(3):729. doi: 10.3390/ijms20030729.