TRPs in the Brain

Abstract

The Transient receptor potential (TRP) family of cation channels is a large protein family, which is mainly structurally uniform. Proteins consist typically of six transmembrane domains and mostly four subunits are necessary to form a functional channel. Apart from this, TRP channels display a wide variety of activation mechanisms (ligand binding, G-protein coupled receptor dependent, physical stimuli such as temperature, pressure, etc.) and ion selectivity profiles (from highly Ca(2+) selective to non-selective for cations). They have been described now in almost every tissue of the body, including peripheral and central neurons. Especially in the sensory nervous system the role of several TRP channels is already described on a detailed level. This review summarizes data that is currently available on their role in the central nervous system. TRP channels are involved in neurogenesis and brain development, synaptic transmission and they play a key role in the development of several neurological diseases.

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

“…In the CNS, TRPA1 modulates glycinergic transmission in synapses of the medullary dorsal horn neurons (Nilius, 2012). In the presynaptic terminals of magnocellular neurosecretory cells that produce vasopressin in the supraoptic nucleus, TRPA1 activation enhances glutamate release and plays a role in the hippocampus (for a review, see Nilius, 2012;Vennekens et al, 2012).…”

“…Despite the plethora of reports on TRP channel expression in the brain (reviewed in Reboreda, 2012;Vennekens et al, 2012), our understanding of the participation of these channels in physiologic functions and disease states is still rudimentary. However, there is no shortage in speculations linking TRP channels to the whole spectrum of neurologic and psychiatric diseases from the common (e.g., stroke, anxiety disorders, and AD) to the esoteric (e.g., Western Pacific ALS-G/dementia complex).…”

Absence of Transient Receptor Potential Vanilloid-1 Accelerates Stress-Induced Axonopathy in the Optic Projection

“…How such signals arise in response to relevant stressors is critical for understanding disease progression and for identifying early molecular targets for therapeutic intervention. The transient receptor potential (TRP) family of cation-selective ion channels mediates a variety of neuronal responses to both physiologic and pathogenic stimuli (Lin and Corey, 2005;Ho et al, 2012;Vennekens et al, 2012). The diversity of different TRP subunits arises in part from the broad spectrum of ligand-based, membranebound, and biophysical mechanisms through which they are activated.…”

Physiological and Pathophysiological Roles of Transient Receptor Potential Channels in Microglia-Related CNS Inflammatory Diseases

“…15) TRPC members are classified into two groups on the basis of their sequence homology and functional similarity: the TRPC1/TRPC4/TRPC5 and TRPC3/TRPC6/ TRPC7 groups. 16) TRPC3, TRPC6, and TRPC7 form the diacylglycerol (DAG)-sensitive group and are activated by DAG after stimulation of phospholipase C (PLC)-coupled receptors such as G q/11 -type G-protein-coupled receptors or receptor tyrosine kinases.…”