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. TRPV subfamily consists of six members viz. TRPV1-6. While the neuroanatomical and functional correlates of TRPV1-4 have been extensively studied, relevant information about TRPV5 and TRPV6, which are highly selective for Ca²⁺, is limited. We detected TRPV5 mRNA expression in the olfactory bulb, cortex, hypothalamus, hippocampus, midbrain, brainstem and cerebellum of rat. TRPV5-immunoreactive neurons were conspicuously seen in the hypothalamic paraventricular (PVN), supraoptic (SON), accessory neurosecretory (ANS), retrochiasmatic area of SON (SOR), arcuate (ARC), medial tuberal nuclei, and specific group of neurons in the 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 whom TRPV5 may co-exist. In hypothalamic neurons, we find the co-expression of TRPV5 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 neurons express estrogen receptors, 17β-estradiol regulates TRPV5, and CART neurons and astrocytes in ARC. Further, ARC CART neurons are known to project to preoptic area, and innervate and regulate GnRH neurons. Using double immunofluorescence, GFAP-labeled astrocytes and majority of CART neurons in ARC showed TRPV5-immunoreactivity. Following iontophoresis of retrograde neuronal tracer, cholera toxin beta (CtB) into the anteroventral periventricular nucleus and median preoptic nucleus, retrograde accumulation of CtB was observed in majority of TRPV5-equipped ARC CART neurons. Next, we determined the response of TRPV5-elements in the ARC during estrous cycle. Compared to proestrus, a significant increase (P<0.001) in the percentage of TRPV5-expressing CART neurons was observed during estrus, metestrus, and diestrus. TRPV5-immunoreactivity in the astrocytes, however, showed a significant increase during metestrus and diestrus. We suggest that TRPV5 ion channel may serve as an important regulator of neural and neuroendocrine pathways in the brain.

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