Investigating Contributions of Canonical Transient Receptor Potential Channel 3 to Hippocampal Hyperexcitability and Seizure-Induced Neuronal Cell Death.

Canonical transient receptor potential channel 3 (TRPC3) is the most abundant TRPC channel in the brain and is highly expressed in all subfields of the hippocampus. Previous studies have suggested that TRPC3 channels may be involved in the hyperexcitability of hippocampal pyramidal neurons and seizures. Genetic ablation of TRPC3 channel expression reduced the intensity of pilocarpine-induced status epilepticus (SE).

Increased Susceptibility to Pilocarpine-Induced Status Epilepticus and Reduced Latency in TRPC1/4 Double Knockout Mice.

Canonical transient receptor potential channels (TRPCs) are a family of calcium-permeable cation channels. Previous studies have shown that heteromeric channels comprising TRPC1 and TRPC4 mediate epileptiform bursting in lateral septal neurons and hippocampal CA1 pyramidal neurons, suggesting that TRPC1/4 channels play a pro-seizure role. In this study, we utilized electroencephalography (EEG) recording and spectral analysis to assess the role of TRPC1/4 channels in the pilocarpine model of status epilepticus (SE).

Pharmacological Differences between Native Homomeric Transient Receptor Potential Canonical Type 4 Channels and Heteromeric Transient Receptor Potential Canonical Type 1/4 Channels in Lateral Septal Neurons.

Given the unique expression patterns and revelations of its critical involvement in a host of neurological disorders, the TRPC1/4/5 subgroup has become an intense target of drug development, and some compounds are now in clinical trials. However, little is known about the exact subunit composition of this subfamily of TRPC channels in various native tissues, and whether it has functional and pharmacological implications. In this study, we investigated the effects of two TRPC4 modulators located in the lateral septum, in which a metabotropic glutamate receptor (mGluR) agonist-induced plateau potential is mediated by TRPC channels composed of TRPC1 and TRPC4.

TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice.

Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy.

Pilocarpine-induced status epilepticus in mice: A comparison of spectral analysis of electroencephalogram and behavioral grading using the Racine scale.

Pilocarpine-induced status epilepticus (SE) is a widely used seizure model in mice, and the Racine scale has been used to index seizure intensity. The goal of this study was to analyze electroencephalogram (EEG) quantitatively using fast Fourier transformation (FFT) and statistically evaluate the correlation of electrographic seizures with convulsive behaviors. Simultaneous EEG and video recordings in male mice in a mixed genetic background were conducted and pilocarpine was administered intraperitoneally to induce seizures.

Critical role of canonical transient receptor potential channel 7 in initiation of seizures.

Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early process leading to the initiation of SE is not well understood.

Canonical transient receptor channel 5 (TRPC5) and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms.

Seizures are the manifestation of highly synchronized burst firing of a large population of cortical neurons. Epileptiform bursts with an underlying plateau potential in neurons are a cellular correlate of seizures. Emerging evidence suggests that the plateau potential is mediated by neuronal canonical transient receptor potential (TRPC) channels composed of members of the TRPC1/4/5 subgroup.

Heteromeric canonical transient receptor potential 1 and 4 channels play a critical role in epileptiform burst firing and seizure-induced neurodegeneration.

Canonical transient receptor potential channels (TRPCs) are receptor-operated cation channels that are activated in response to phospholipase C signaling. Although TRPC1 is ubiquitously expressed in the brain, TRPC4 expression is the most restrictive, with the highest expression level limited to the lateral septum. The subunit composition of neuronal TRPC channels remains uncertain because of conflicting data from recombinant expression systems.