Transient receptor potential vanilloid 5 (TRPV5), a highly Ca²⁺‐selective TRP channel in the rat brain: relevance to neuroendocrine regulation

Abstract

Recent studies suggest an important role for transient receptor potential vanilloid (TRPV) ion channels in neural and neuroendocrine regulation. The TRPV subfamily consists of six members: TRPV1-6. While the neuroanatomical and functional correlates of TRPV1-4 have been studied extensively, relevant information about TRPV5 and TRPV6, which are highly selective for Ca , is limited. We detected TRPV5 mRNA expression in the olfactory bulb, cortex, hypothalamus, hippocampus, midbrain, brainstem and cerebellum of the rat. TRPV5-immunoreactive neurones were conspicuously seen in the hypothalamic paraventricular (PVN), supraoptic (SON), accessory neurosecretory (ANS), supraoptic nucleus, retrochiasmatic part (SOR), arcuate (ARC) and medial tuberal nuclei, hippocampus, midbrain, brainstem and cerebellum. Glial cells also showed TRPV5-immunoreactivity. To test the neuroendocrine relevance of TRPV5, we focused on vasopressin, oxytocin and cocaine- and amphetamine-regulated transcript (CART) as representative candidate markers with which TRPV5 may co-exist. In the hypothalamic neurones, co-expression of TRPV5 was observed with vasopressin (PVN: 50.73±3.82%; SON: 75.91±2.34%; ANS: 49.12±4.28%; SOR: 100%) and oxytocin (PVN: 6.88±1.21; SON: 63.34±5.69%; ANS: 20.4±4.14; SOR: 86.5±1.74%). While ARC neurones express oestrogen receptors, 17β-oestradiol regulates TRPV5, as well as CART neurones and astrocytes, in the ARC. Furthermore, ARC CART neurones are known to project to the preoptic area, and innervate and regulate GnRH neurones. Using double-immunofluorescence, glial fibrillary acidic protein-labelled astrocytes and the majority of CART neurones in the ARC showed TRPV5-immunoreactivity. Following iontophoresis of retrograde neuronal tracer, cholera toxin β (CtB) into the anteroventral periventricular nucleus and median preoptic nucleus, retrograde accumulation of CtB was observed in most TRPV5-equipped ARC CART neurones. Next, we determined the response of TRPV5-elements in the ARC during the oestrous cycle. Compared to pro-oestrus, a significant increase (P<.001) in the percentage of TRPV5-expressing CART neurones was observed during oestrus, metoestrus, and dioestrus. TRPV5-immunoreactivity in the astrocytes, however, showed a significant increase during metoestrus and dioestrus. We suggest that the TRPV5 ion channel may serve as an important regulator of neural and neuroendocrine pathways in the brain.

Ion Channels in the Paraventricular Hypothalamic Nucleus (PVN); Emerging Diversity and Functional Roles

“…TRPV5 has been observed in both neurones and glia, although the role of TRPV5 in glia is yet to be established. This study showed TRPV5 expression in a remarkable ∼50% of vasopressin neurones and ∼6–7% of oxytocin neurones in the rat PVN ( Kumar et al, 2017 ). It is therefore likely that TRPV2 and TRPV5 work in a coordinated fashion in the maintenance of endocrine homeostasis.…”

“…Since oxytocin appears to have other roles too, it will be interesting to discover if they too are mediated by TRPV2. It is quite likely that in native tissue, combinations of different ion channels are involved with any given response and this is emphasized by similar data showing TRPV5 mediated oxytocin (and vasopressin) responses ( Kumar et al, 2017 ). This TRPV5 expression study used immunohistochemistry and target verification with siRNA knock-down of the channel ( Kumar et al, 2017 ).…”

“…It is quite likely that in native tissue, combinations of different ion channels are involved with any given response and this is emphasized by similar data showing TRPV5 mediated oxytocin (and vasopressin) responses ( Kumar et al, 2017 ). This TRPV5 expression study used immunohistochemistry and target verification with siRNA knock-down of the channel ( Kumar et al, 2017 ). TRPV5 has been observed in both neurones and glia, although the role of TRPV5 in glia is yet to be established.…”

The role of TRP channels in white matter function and ischaemia

“…TRPV5 is primarily expressed in kidney epithelial cells, however it is also expressed at lower levels in the brain. Immunolabelling for TRPV5 indicates it is expressed in neurons and astrocytes [101]. In the arcuate nucleus, TRPV5 expression in astrocytes seems to be regulated by 17-oestradiol or ischaemia, where it can cause a detrimental Ca 2+ concentration rise [101].…”

TRP Ion Channels: From Distribution to Assembly

“…TRPV1 has been detected in mammalian brain, especially one study revealed that TRPV1 exhibited highly restricted distribution in central neuronal system in rat, monkey and human by using in situ hybridization as well as electrophysiological recordings [3]. Recent studies reported that TRPV5 was detected in olfactory bulb, cortex, hippocampus, hypothalamus, midbrain, brainstem and cerebellum of the rat [4]. In addition, TRPV6 was found in lamina terminalis, olfactory bulb, amygdala, hippocampus, brainstem and cerebellum of the mouse [5].…”