Cellular subtype distribution and developmental regulation of TRPC channel members in the mouse dorsal root ganglion

Abstract

Transient receptor potential (TRP) channels play essential roles in sensory physiology and their expression in different classes of sensory neurons reflect distinct receptive properties of these neurons. While expression of the TRPV, TRPA, and to a certain degree TRPM classes of channels has been studied in sensory neurons, little is known about the expression and regulation of TRPC channels. In this study we examined the regulation of all TRPC members (TRPC1-C7) throughout embryonic and postnatal development of the dorsal root ganglion (DRG) and nodose ganglion (NG). In adult mice, mRNAs for all channels were present in the DRG, with TRPC1, 3, and 6 being the most abundant, TRPC2, C4, and C5 at lower levels, and TRPC7 at very low levels. While TRPC2 mRNAs were downregulated from high levels at embryonic (E) day 12 and E14 until adult, TRPC4, C5, and C7 expressions increased from E12 to peak levels at E18. TRPC1, C3, and C6, the most abundant TRPC channel mRNAs, increased progressively from E12 to adult. Expression and regulation of TRPC channels mRNAs in the NG were unexpectedly similar to the DRG. TRPC1 and C2 was expressed in the neurofilament-200 (NF-200)-positive large size subclass of neurons, while TRPC3 mRNAs expression, which stained up to 35% of DRG neurons, was almost exclusively present in nonpeptidergic isolectin B4 (IB4)-positive small size neurons that were largely TRPV1-negative. Our results suggest important roles of the TRPC family of channels in sensory physiology of both nociceptive as well as nonnociceptive classes of neurons.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…For instance, TRPV1 appears to be widely expressed in neonatal (Ritter and Dinh, 1992), but not adult (Cavanaugh et al, 2011), mouse brain. Furthermore, TRPC1, TRPC3, and TRPC6 are highly expressed in adult, but not neonatal, rodent DRG neurons; by contrast, TRPC2 and TRPC5 show an age-dependent decline in expression levels (Elg et al, 2007).…”

“…Maybe because they are ubiquitously expressed, the presence of TRPC channels in sensory neurons has attracted little attention (Elg et al, 2007). In adult mice, all seven members of the TRPC family (TRPC1-TRPC7) were detected in DRG neurons with TRPC1, TRPC3, and TRPC6 being the most abundant.…”

Early Emergence of Neural Activity in the Developing Mouse Enteric Nervous System

“…In the adult ENS, N-, P/Q-, L-and R-type Ca 2ϩ currents have been recorded, mostly from guinea pig myenteric neurons (Kirchgessner and Liu, 1999;Starodub and Wood, 1999;Reis et al, 2000;Bian and Galligan, 2007 (Talavera et al, 2008). Several TRP channels are expressed in the mature ENS (Boesmans et al, 2011) and also in parts of the developing mammalian nervous system that are also of neural crest origin, including embryonic dorsal root ganglion neurons (Tamura et al, 2005;Elg et al, 2007). In particular, the role of canonical TRP (TRPC) channels, which mediate guidance of growth cones and survival of neurons in response to chemical cues such as neurotrophins (Talavera et al, 2008), is worth pursuing.…”

Biphasic modulation of noxious heat sensitivity in sensory neurons by peripheral metabotropic glutamate receptors

“…Interestingly, in the central nervous system, such as the cerebellum, striatum etc., mGluR1/5 are functionally coupled with other TRP channels, such as TRPC1 and TRPC3/7 [14,15] , which are also expressed by DRG neurons [16] . It is likely that the interactions between group I mGluRs and TRP channels have low specificity, which may enable easy switching between coupled molecules with variable cellular conditions, such as channels, enzyme and scaffold protein expression.…”