Functional Expression of an Osmosensitive Cation Channel, Transient Receptor Potential Vanilloid 4, in Rat Vestibular Ganglia

Abstract

Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca²⁺) imaging of VG neurons showed that 4α-PDD and/or hypotonic stimuli caused an increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca²⁺]_i increase was evoked by both hypotonic stimuli and 4α-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor.

The emerging role of transient receptor potential channels in chronic lung disease

“…arachidonic acid derivatives, changes in osmolarity, endocannabinoids, α-phorbols, proteases and mechanical stimuli) [74][75][76]. TRPV4 mRNA expression has been demonstrated in rodent sensory, trigeminal, dorsal root, vestibular, nodose and jugular ganglia [8,9,[77][78][79][80][81]. However, expression studies were performed on whole ganglia rather than single-cell expression studies on isolated neurons, so expression on non-neuronal cells cannot be ruled out.…”

Nutrient‐induced hyperosmosis evokes vasorelaxation via TRPV1 channel‐mediated, endothelium‐dependent, hyperpolarisation in healthy and colitis mice

“…Previous studies have reported that intraduodenal infusion of glucose in healthy subjects could significantly increase superior mesenteric artery blood flow, and it had been assumed that acute application of glucose and sodium could induce vasorelaxation of mesenteric artery, most likely through NO production (Matheson et al, 1997;Qu et al, 2014;Zani & Bohlen, 2005). However, it is currently accepted that NO mainly regulates the tone of large conduit vessels, whereas EDH plays a dominant role in small resistance vessels such as mesenteric and cardiac arterioles (Crane, Gallagher, Dora, & Garland, 2003;Garland et al, 1995;Godo et al, 2016 (Ma et al, 2013;Seki et al, 2017), and they are osmosensitive or mechanosensitive (Adapala et al, 2016;Kamakura et al, 2016). We initially tested if endothelial TRPV4/Ca 2+ signalling is involved in hyperosmosis-induced EDH signals.…”

“…Since the EDH‐associated SK Ca and IK Ca channels in vascular endothelial cells are sensitive to [Ca 2+ ] i , we examined their mechanism of activation. It is well known that the Ca 2+ ‐permeable TRPV1 and TRPV4 channels are functionally expressed in HUVECs (Ma et al, 2013; Seki et al, 2017), and they are osmosensitive or mechanosensitive (Adapala et al, 2016; Kamakura et al, 2016). We initially tested if endothelial TRPV4/Ca 2+ signalling is involved in hyperosmosis‐induced EDH signals.…”