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Epilepsy is characterized by spontaneous seizures. Changes in the expression of the connexins (Cxs) have been reported to be involved in epileptogenesis. It has previously been shown that the transient receptor potential vanilloid 4 (TRPV4) plays an important role in the modulation of neuronal excitability, and that application of a TRPV4 antagonist blocks hyperthermia-induced seizures. Accordingly, in the present study, we sought to explore whether TRPV4 is involved in the regulation of Cx expression following pilocarpine-induced status epilepticus (PISE) in mice. We observed that TRPV4 protein levels in hippocampi increased 3 h to 30 d following PISE, peaking 1 to 3 d after induction, and that pre-application of the TRPV4 antagonist HC-067047 increased the latency to develop SE induced by pilocarpine and reduced the success rate of PISE preparation. We demonstrated that Cx43 protein levels followed a time profile similar to that of TRPV4, and further showed that the increase in Cx43 protein levels on 3 d post-PISE was markedly attenuated by HC-067047. In contrast, the corresponding increase in Cx32 protein levels lagged substantially behind, and these levels were unaffected by HC-067047. Similarly, the TRPV4 agonist GSK1016790A increased the mRNA and protein levels of Cx43, but not those of Cx32. We thus conclude that the upregulation of Cx43 expression by TRPV4 may be involved in the pathophysiology of epilepsy.
This article was published in the following journal.
Name: Brain research bulletin
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A gap junction beta subunit that forms heteromeric hemichannels when paired with alpha subunits such as connexin-40 or CONNEXIN 43. Mutations in the connexin 30 gene (GJ6B) are associated with CLOUSTON'S SYNDROME and some hereditary forms of deafness.
A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain.
A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.
A gap junction protein encoded by the Gap Junction Beta 2 or GJB2 gene. In the cochlea and epidermis, its hexamers form channels between cells that open to allow cell-to-cell diffusion of small molecules as well as recycling of potassium. Mutations in Connexin 26 are associated with congenital SENSORINEURAL HEARING LOSS.
A nuclear protein that regulates the expression of genes involved in a diverse array of processes related to metabolism and reproduction. The protein contains three nuclear receptor interaction domains and three repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 2.
Neurology - Central Nervous System (CNS)
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