Corticolimbic Expression of TRPC4 and TRPC5 Channels in the Rodent Brain

Abstract

The canonical transient receptor potential (TRPC) channels are a family of non-selective cation channels that are activated by increases in intracellular Ca2+ and Gq/phospholipase C-coupled receptors. We used quantitative real-time PCR, in situ hybridization, immunoblots and patch-clamp recording from several brain regions to examine the expression of the predominant TRPC channels in the rodent brain. Quantitative real-time PCR of the seven TRPC channels in the rodent brain revealed that TRPC4 and TRPC5 channels were the predominant TRPC subtypes in the adult rat brain. In situ hybridization histochemistry and immunoblotting further resolved a dense corticolimbic expression of the TRPC4 and TRPC5 channels. Total protein expression of HIP TRPC4 and 5 proteins increased throughout development and peaked late in adulthood (6–9 weeks). In adults, TRPC4 expression was high throughout the frontal cortex, lateral septum (LS), pyramidal cell layer of the hippocampus (HIP), dentate gyrus (DG), and ventral subiculum (vSUB). TRPC5 was highly expressed in the frontal cortex, pyramidal cell layer of the HIP, DG, and hypothalamus. Detailed examination of frontal cortical layer mRNA expression indicated TRPC4 mRNA is distributed throughout layers 2–6 of the prefrontal cortex (PFC), motor cortex (MCx), and somatosensory cortex (SCx). TRPC5 mRNA expression was concentrated specifically in the deep layers 5/6 and superficial layers 2/3 of the PFC and anterior cingulate. Patch-clamp recording indicated a strong metabotropic glutamate-activated cation current-mediated depolarization that was dependent on intracellular Ca2+and inhibited by protein kinase C in brain regions associated with dense TRPC4 or 5 expression and absent in regions lacking TRPC4 and 5 expression. Overall, the dense corticolimbic expression pattern suggests that these Gq/PLC coupled nonselective cation channels may be involved in learning, memory, and goal-directed behaviors.

TRPC4 ion channel protein is selectively expressed in a subpopulation of dopamine neurons in the ventral tegmental area

“…The localization of TRPC4 in the adult rat brain is consistent with previous in situ mRNA 1 . In this study we increased the resolution of the TRPC4 mRNA and protein to the cellular level and discovered selective co-localization of TRPC4 channels in subpopulations of TH-positive DA neurons.…”

“…The TRPC family of nonselective channels are made up of seven members (TRPC1-7) and the TRPC4 channel is one of the two most abundant in the mammalian brain 1 . Our recent findings indicate that the TRPC4 channel is important for sociability in a rodent model of social interaction 3 .…”

Identification of ML204, a Novel Potent Antagonist That Selectively Modulates Native TRPC4/C5 Ion Channels

“…TRPC4 and TRPC5 are abundantly expressed in smooth muscle and central nervous system, but these expression patterns do not perfectly overlap (29,30). TRPC channels can function as both homo-and heterotetramers with a preference of heteromultimerization among members of the same TRPC subgroup, as well as TRPC1 with TRPC4/C5 (31-33).…”

Transient Receptor Potential Canonical Channels Regulate the Induction of Cerebellar Long-Term Depression

“…While SKF96365 has been used extensively as a tool to define the functional roles of TRPC channels in various cell and tissue types (Bengtson et al, 2004;Fowler et al, 2007), previous studies reported notable overlapping effects on numerous channels in various organs (Merritt et al, 1990;Hong and Chang, 1994;Schwarz et al, 1994;Juvin et al, 2007;Liu et al, 2007). A high concentration of SKF96365 (30 M) partly affected low voltageactivated T-type calcium channels in Purkinje cells (Singh et al, 2010).…”