Transient Receptor Potential channels

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).


« Hide More detailed introduction

The TRP superfamily of channels (nomenclature agreed by NC-IUPHAR; [25,181]), whose founder member is the Drosophila Trp channel, exists in mammals as six families; TRPC, TRPM, TRPV, TRPA, TRPP and TRPML based on amino acid homologies. TRP subunits contain six putative transmembrane domains and assemble as homo- or hetero-tetramers to form cation selective channels with diverse modes of activation and varied permeation properties (reviewed by [126]). Established, or potential, physiological functions of the individual members of the TRP families are discussed in detail in the recommended reviews and a compilation edited by Islam [64]. The established, or potential, involvement of TRP channels in disease is reviewed in [74,116] and [117], together with a special edition of Biochemica et Biophysica Acta on the subject [116]. The pharmacology of most TRP channels is poorly developed [181]. Broad spectrum agents are listed in the tables along with more selective, or recently recognised, ligands that are flagged by the inclusion of a primary reference. Most TRP channels are regulated by phosphoinostides such as PtIns(4,5)P2 and IP3 although the effects reported are often complex, occasionally contradictory, and likely be dependent upon experimental conditions (reviewed by [118,143,169]). Such regulation is generally not included in the tables.

TRPA (ankyrin) family

TRPA1 is the sole mammalian member of this group (reviewed by [41]). In some [6,69,147,155], but not other [66,111], studies TRPA1 is activated by noxious cold. One study suggests that activation of TRPA1 is secondary to a cold-induced elevation of [Ca2+]i [192], but this has been refuted [69]. Additionally, TRPA1 has been proposed to be a component of a mechanosensitive transduction channel of vertebrate hair cells [27,111], but TRPA1(-/-) mice demonstrate no impairment in hearing, or vestibular function [11,84]. There is consensus that TRPA1 acts as a nociceptor for environmental irritants [8].

TRPC (canonical) family

Members of the TRPC subfamily (reviewed by [1-2,15,18,40,72,129,139]) fall into the subgroups outlined below. TRPC2 (not tabulated) is a pseudogene in man. It is generally accepted that all TRPC channels are activated downstream of Gq/11-coupled receptors, or receptor tyrosine kinases (reviewed by [136,163,181]). A comprehensive listing of G-protein coupled receptors that activate TRPC channels is given in [1]. Hetero-oligomeric complexes of TRPC channels and their association with proteins to form signalling complexes are detailed in [2] and [73]. TRPC channels have frequently been proposed to act as store-operated channels (SOCs) (or compenents of mulimeric complexes that form SOCs), activated by depletion of intracellular calcium stores (reviewed by [2,22,130,137,146,187]), but this is controversial. All members of the TRPC family are blocked by 2-APB and SKF96365 [53-54]. Activation of TRPC channels by lipids is discussed by [15].

TRPC1/C4/C5 subgroup
TRPC4/C5 may be distinguished from other TRP channels by their potentiation by micromolar concentrations of La3+.

TRPC3/C6/C7 subgroup
All members are activated by diacylglycerol independent of protein kinase C stimulation [54].

TRPM (melastatin) family

Members of the TRPM subfamily (reviewed by [38,53,130,189]) fall into the five subgroups outlined below.

TRPM1/M3 subgroup
TRPM1 exists as five splice variants and is involved in normal melanocyte pigmentation [122] and is also a visual transduction channel in retinal ON bipolar cells [79]. TRPM3 (reviewed by [124]) exists as multiple splice variants four of which (mTRPM3α1, mTRPM3α2, hTRPM3a and hTRPM31325) have been characterised and found to differ significantly in their biophysical properties. TRPM3 has recently been found to contribute to the detection of noxious heat [173].

TRPM2 functions as a sensor of redox status in cells and is also activated by heat (reviewed by [186]). Numerous splice variants of TRPM2 exist which differ in their activation mechanisms [35].

TRPM4/5 subgroup
TRPM4 and TRPM5 are thermosensitive and have the distinction within all TRP channels of being impermeable to Ca2+ [181]. A splice variant of TRPM4 (i.e.TRPM4b) and TRPM5 are molecular candidates for endogenous calcium-activated cation (CAN) channels [47]. TRPM4 has been shown to be an important regulator of Ca2+ entry in to mast cells [165] and dendritic cell migration [9]. TRPM5 in taste receptor cells of the tongue appears essential for the transduction of sweet, amino acid and bitter stimuli [93].

TRPM6/7 subgroup
TRPM6 and 7 combine channel and enzymatic activities (‘chanzymes’) and are involved in Mg2+ homeostasis (reviewed by [10,132,144]).

Is a channel activated by cooling and pharmacological agents evoking a ‘cool’ sensation and participates in the thermosensation of cold temperatures [13,26,33] reviewed by [78,95,109,170].

TRPML (mucolipin) family

The TRPML family [138,140,188] consists of three mammalian members (TRPML1-3). TRPML channels are probably restricted to intracellular vesicles and mutations in the gene (MCOLN1) encoding TRPML1 (mucolipin-1) are the cause of the neurodegenerative disorder mucolipidosis type IV (MLIV) in man. TRPML1 is a cation selective ion channel that is important for sorting/transport of endosomes in the late endocytotic pathway and specifically fusion between late endosome-lysosome hybrid vesicles. TRPML2 (MCLN2) remains to be functionally characterised in detail. TRPML3 is important for hair cell maturation, stereocilia maturation and intracellular vesicle transport. A naturally occurring gain of function mutation in TRPML3 (i.e. A419P) results in the varitint waddler (Va) mouse phenotype (reviewed by [119,140]).

TRPP (polycystin) family

The TRPP family (reviewed by [30,32,42,59,179]) subsumes the polycystins that are divided into two structurally distinct groups, polycystic kidney disease 1-like (PKD1-like) and polycystic kidney disease 2-like (PKD2-like). Members of the PKD1-like group, in mammals, include PKD1 (reclassified as TRPP1), PDKREJ, PKD1L1, PKD1L2 and PKD1L3. The PKD2-like members comprise PKD2, PKD2L1 and PKD2L2, which have renamed TRPP2, TRPP3 and TRPP5, respectively [106]. PKDREJ (Q9NTG1), PKD1L1 (Q8TDX9), mouse PKD1L2 (Q7TN88), PKD1L3 (Q7Z443) and TRPP5 (PKD2L2, Q9NZM6) are not listed in the table due to lack of functional data. Similarly, TRPP1 (P98161) is also omitted because although one study [5] has reported the induction of a cation conductance in CHO cells transfected with TRPP1, there is no unequivocal evidence that TRPP1 is a channel per se and in other studies (e.g. [31,51]) TRPP1 is incapable of producing currents.

TRPV (vanilloid) family

Members of the TRPV family (reviewed by [166]) can broadly be divided into the theromosensitive, non-selective cation channels, TRPV1-4 and the calcium selective channels TRPV5 and TRPV6.

TRPV1-V4 subfamily
TRPV1 is involved in the development of thermal hyperalgesia following inflammation and may contribute to the detection of noxius heat (reviewed by [135,154,158]). Numerous splice variants of TRPV1 have been described, some of which modulate the activity of TRPV1, or act in a dominant negative manner when co-expressed with TRPV1 [148]. The pharmacology of TRPV1 channels is discussed in detail in [49] and [172]. TRPV2 is probably not a thermosensor in man [127], but has recently been implicated in innate immunity [94]. TRPV3 and TRPV4 are both thermosensitive, with the latter also having a mechanosensing function [36].

TRPV5/V6 subfamily
Under physiological conditions, TRPV5 and TRPV6 are calcium selective channels involved in the absorption and reabsorption of calcium across intestinal and kidney tubule epithelia (reviewed by [29,178]).


TRPA1 Show summary » More detailed page

TRPC1 Show summary » More detailed page

TRPC2 Show summary » More detailed page

TRPC3 Show summary » More detailed page

TRPC4 Show summary » More detailed page

TRPC5 Show summary » More detailed page

TRPC6 Show summary » More detailed page

TRPC7 Show summary » More detailed page

TRPM1 Show summary » More detailed page

TRPM2 Show summary » More detailed page

TRPM3 Show summary » More detailed page

TRPM4 Show summary » More detailed page

TRPM5 Show summary » More detailed page

TRPM6 Show summary » More detailed page

TRPM7 Show summary » More detailed page

TRPM8 Show summary » More detailed page

TRPML1 Show summary » More detailed page

TRPML2 Show summary » More detailed page

TRPML3 Show summary » More detailed page

TRPP1 Show summary » More detailed page

TRPP2 Show summary » More detailed page

TRPP3 Show summary » More detailed page

TRPV1 Show summary » More detailed page

TRPV2 Show summary » More detailed page

TRPV3 Show summary » More detailed page

TRPV4 Show summary » More detailed page

TRPV5 Show summary » More detailed page

TRPV6 Show summary » More detailed page


Show »

Further reading

Show »


Show »

NC-IUPHAR subcommittee and family contributors

Show »

How to cite this family page

Database page citation:

Transient Receptor Potential channels. Accessed on 18/04/2014. IUPHAR/BPS Guide to PHARMACOLOGY,

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Catterall WA, Spedding M, Peters JA and Harmar AJ, CGTP Collaborators. (2013) The Concise Guide to PHARMACOLOGY 2013/14: Ion Channels. Br J Pharmacol. 170: 1607–1651.