TRPCs, GPCRs and the Bayliss effect

An increase in pressure inside most small arteries unexpectedly results in a vasoconstriction. This phenomenon, known as the Bayliss effect, involves the stretch-induced activation of non-selective cation channels in the vascular smooth muscle cells. Recent work by Mederos y Schnitzler et al. now demonstrates that the stretch-induced channel activity originates from a fascinating interplay between a TRP cation channel and the angiotensin receptor.status: publishe

Phosphoinositide regulation of TRPM channels: TRPM3 joins the club!

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Mg2+-dependent Gating and Strong Inward Rectification of the Cation Channel TRPV6

TRPV6 (CaT1/ECaC2), a highly Ca2+-selective member of the TRP superfamily of cation channels, becomes permeable to monovalent cations in the absence of extracellular divalent cations. The monovalent currents display characteristic voltage-dependent gating and almost absolute inward rectification. Here, we show that these two features are dependent on the voltage-dependent block/unblock of the channel by intracellular Mg2+. Mg2+ blocks the channel by binding to a site within the transmembrane electrical field where it interacts with permeant cations. The block is relieved at positive potentials, indicating that under these conditions Mg2+ is able to permeate the selectivity filter of the channel. Although sizeable outward monovalent currents were recorded in the absence of intracellular Mg2+, outward conductance is still ∼10 times lower than inward conductance under symmetric, divalent-free ionic conditions. This Mg2+-independent rectification was preserved in inside-out patches and not altered by high intracellular concentrations of spermine, indicating that TRPV6 displays intrinsic rectification. Neutralization of a single aspartate residue within the putative pore loop abolished the Mg2+ sensitivity of the channel, yielding voltage-independent, moderately inwardly rectifying monovalent currents in the presence of intracellular Mg2+. The effects of intracellular Mg2+ on TRPV6 are partially reminiscent of the gating mechanism of inwardly rectifying K+ channels and may represent a novel regulatory mechanism for TRPV6 function in vivo

Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

Abstract Background Somatosensory nerve fibres arising from cell bodies within the trigeminal ganglia (TG) in the head and from a string of dorsal root ganglia (DRG) located lateral to the spinal cord convey endogenous and environmental stimuli to the central nervous system. Although several members of the transient receptor potential (TRP) superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. Results Here, we used quantitative real-time PCR to analyse and compare mRNA expression of all TRP channels in TG and individual DRGs from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1 and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8 and TRPV1, showed statistically significant variation in mRNA levels between DRGs from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. These ganglion-to-ganglion differences in TRP channel transcript levels may contribute to the variability in sensory responses in functional studies. Conclusions We developed, compared and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channel genes at the single ganglion level. This study also provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family.</p

Ultra-high-field fMRI reveals a role for the subiculum in scene perceptual discrimination

Recent “representational” accounts suggest a key role for the hippocampus in complex scene perception. Due to limitations in scanner field strength, however, the functional neuroanatomy of hippocampal-dependent scene perception is unknown. Here, we applied 7 T high-resolution functional magnetic resonance imaging (fMRI) alongside a perceptual oddity task, modified from nonhuman primate studies. This task requires subjects to discriminate highly similar scenes, faces, or objects from multiple viewpoints, and has revealed selective impairments during scene discrimination following hippocampal lesions. Region-of-interest analyses identified a preferential response in the subiculum subfield of the hippocampus during scene, but not face or object, discriminations. Notably, this effect was in the anteromedial subiculum and was not modulated by whether scenes were subsequently remembered or forgotten. These results highlight the value of ultra-high-field fMRI in generating more refined, anatomically informed, functional accounts of hippocampal contributions to cognition, and a unique role for the human subiculum in discrimination of complex scenes from different viewpoints

Comparing ion conductance recordings of synthetic lipid bilayers with cell membranes containing TRP channels

In this article we compare electrical conductance events from single channel recordings of three TRP channel proteins (TRPA1, TRPM2 and TRPM8) expressed in human embryonic kidney cells with channel events recorded on synthetic lipid membranes close to melting transitions. Ion channels from the TRP family are involved in a variety of sensory processes including thermo- and mechano-reception. Synthetic lipid membranes close to phase transitions display channel-like events that respond to stimuli related to changes in intensive thermodynamic variables such as pressure and temperature. TRP channel activity is characterized by typical patterns of current events dependent on the type of protein expressed. Synthetic lipid bilayers show a wide spectrum of electrical phenomena that are considered typical for the activity of protein ion channels. We find unitary currents, burst behavior, flickering, multistep-conductances, and spikes behavior in both preparations. Moreover, we report conductances and lifetimes for lipid channels as described for protein channels. Non-linear and asymmetric current-voltage relationships are seen in both systems. Without further knowledge of the recording conditions, no easy decision can be made whether short current traces originate from a channel protein or from a pure lipid membraneComment: 13 pages, 9 Figure