PMID- 34113237
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210612
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 15
DP  - 2021
TI  - Overexpressed Na (V) 1.7 Channels Confer Hyperexcitability to in vitro Trigeminal 
      Sensory Neurons of Ca (V) 2.1 Mutant Hemiplegic Migraine Mice.
PG  - 640709
LID - 10.3389/fncel.2021.640709 [doi]
LID - 640709
AB  - Trigeminal sensory neurons of transgenic knock-in (KI) mice expressing the R192Q 
      missense mutation in the alpha1A subunit of neuronal voltage-gated Ca (V) 2.1 Ca(2+) 
      channels, which leads to familial hemiplegic migraine type 1 (FHM1) in patients, 
      exhibit a hyperexcitability phenotype. Here, we show that the expression of Na 
      (V) 1.7 channels, linked to pain states, is upregulated in KI primary cultures of 
      trigeminal ganglia (TG), as shown by increased expression of its alpha1 subunit. In 
      the majority of TG neurons, Na (V) 1.7 channels are co-expressed with ATP-gated 
      P2X3 receptors (P2X3R), which are important nociceptive sensors. Reversing the 
      trigeminal phenotype with selective Ca (V) 2.1 channel inhibitor omega-agatoxin IVA 
      inhibited Na (V) 1.7 overexpression. Functionally, KI neurons revealed a 
      TTX-sensitive inward current of larger amplitude that was partially inhibited by 
      selective Na (V) 1.7 blocker Tp1a. Under current-clamp condition, Tp1a raised the 
      spike threshold of both wild-type (WT) and KI neurons with decreased firing rate 
      in KI cells. Na (V) 1.7 activator OD1 accelerated firing in WT and KI neurons, a 
      phenomenon blocked by Tp1a. Enhanced expression and function of Na (V) 1.7 
      channels in KI TG neurons resulted in higher excitability and facilitated 
      nociceptive signaling. Co-expression of Na (V) 1.7 channels and P2X3Rs in TGs may 
      explain how hypersensitivity to local stimuli can be relevant to migraine.
CI  - Copyright (c) 2021 Mehboob, Marchenkova, van den Maagdenberg and Nistri.
FAU - Mehboob, Riffat
AU  - Mehboob R
AD  - Department of Neuroscience, International School for Advanced Studies (SISSA), 
      Trieste, Italy.
AD  - Research Unit, Faculty of Allied Health Sciences, University of Lahore, Lahore, 
      Pakistan.
FAU - Marchenkova, Anna
AU  - Marchenkova A
AD  - Department of Neuroscience, International School for Advanced Studies (SISSA), 
      Trieste, Italy.
FAU - van den Maagdenberg, Arn M J M
AU  - van den Maagdenberg AMJM
AD  - Department of Neurology, Leiden University Medical Center, Leiden, Netherlands.
AD  - Department of Human Genetics, University Medical Center, Leiden, Netherlands.
FAU - Nistri, Andrea
AU  - Nistri A
AD  - Department of Neuroscience, International School for Advanced Studies (SISSA), 
      Trieste, Italy.
LA  - eng
PT  - Journal Article
DEP - 20210525
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC8185157
OTO - NOTNLM
OT  - calcium channel
OT  - migraine
OT  - nociception
OT  - purinergic receptors
OT  - sodium channel
OT  - transgenic mice
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/12 06:00
MHDA- 2021/06/12 06:01
PMCR- 2021/01/01
CRDT- 2021/06/11 06:42
PHST- 2020/12/11 00:00 [received]
PHST- 2021/04/09 00:00 [accepted]
PHST- 2021/06/11 06:42 [entrez]
PHST- 2021/06/12 06:00 [pubmed]
PHST- 2021/06/12 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2021.640709 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2021 May 25;15:640709. doi: 10.3389/fncel.2021.640709. 
      eCollection 2021.