TRPM3 | Transient Receptor Potential Cation Channel Subfamily M Member 3
Family:
Transient receptor potential channels
Subgroups:
TRPC (TRPC1–TRPC7), TRPV (TRPV1-TRPV6), TRPA1, TRPM (TRPM1–TRPM8), TRPP (TRPP1–TRPP3, PKD1, PKDREJ, PKDL1–PKDL3), TRPML (TRPML1–TRPML3), TRPN
Topology:
Most TRP channels are composed of 6 transmembrane domains (helices) with intracellular N- and C-termini, non-selectively permeable to various cations
TRPM3: Background information
TRPM3, also called Long Transient Receptor Potential Channel 3, is a cation-selective channel important for cellular calcium signaling and homeostasis. TRPM3 mediates calcium entry, and this entry is potentiated by calcium store depletion. Its activity is increased by reduction in extracellular osmolarity, by store depletion and muscarinic receptor activation. TRPM3 was shown to be activated by the neurosteroid pregnenolone sulphate in pancreatic beta cell. The activation causes calcium influx and subsequent insulin release, therefore it is suggested that TRPM3 modulates glucose homeostasis.
Gene:
TRPM3
Human Protein:
UniProt Q9HCF6
Tissue:
Kidney, brain, testis, ovary, pancreas, spinal cord
Function/ Application:
Glucose hemostase, calcium entry into cells upon calcium store depletion, renal calcium homeostasis
Pathology:
Dentin sensitivity, Chronic Fatigue Syndrome.
Interaction:
Oncostatin M, Actin, alpha 2
Modulator:
Nifedipine, mefenamic acid, pioglitazone, sphingosine, pregnenolone sulphate
Assays:
Patch Clamp: whole cell
Recommended Reviews:International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels., Pharmacol Rev 55(4):591-6 Clapham, et al. 2003
Data and Applications
TRPM3 - Positive modulation
Patchliner data and applications:
Cells were kindly provided by Prof. Thomas Voets, KU Leuven, Belgium.
A Current responses to a voltage ramp protocol from -150 mV to 150 mV over 200 ms in response to 100 μM pregnenolone sulphate (PS) and in combination with increasing concentrations of compound C. B Current responses elicited by PS, enhancement by 30 μM compound C and block of the current by co-application of antagonist (10 μM).
TRPM3 - Pharmacology
Patchliner data and applications:
Data are taken from Naylor J. et al., British Journal of Pharmacology, 2008, 1-7.
Shown are whole cell currents as responses to 0.2 s voltage ramps (−100 mV to +100 mV) which were applied every 10 s. All cells were HEK293 cells induced to express TRPM3. (a and c) Mean currents sampled at −80 and +80 mV, each normalized to the amplitude immediately before bath application of antiserum (TM3E3; 1:500 dilution) without (a, n = 8) or with (c, n = 4) pre-adsorption to 10 μM antigenic peptide. Pregnenolone sulphate (PregS) was bath applied at 25 μM. (b and d) Typical current voltage relationships from the experiments underlying (a) and (c).
Publications
2011 - Rapid and Contrasting Effects of Rosiglitazone on Transient Receptor Potential TRPM3 and TRPC5 Channels
Patchliner publication in Molecular Pharmacology (2011)
Authors:
Majeed Y., Bahnasi Y., Seymour V.A.L., Wilson L.A., Milligan C.J., Agarwal A.K., Sukumar P., Naylor J., Beech D.J.
2010 - Pregnenolone Sulphate- and Cholesterol-Regulated TRPM3 Channels Coupled to Vascular Smooth Muscle Secretion and Contraction
Patchliner publication in Circulation Research (2010)
Authors:
Naylor J., Li J., Milligan C.J, Zeng F., Sukumar P., Hou B., Sedo A., Yuldasheva N., Majeed Y., Beri D., Jiang S., Seymour V.A.L, McKeown L., Kumar B., Harteneck C., O'Regan D., Wheatcroft S.B., Kearney M.T, Jones C., Porter K.E., Beech D.J.
2008 - Production of a specific extracellular inhibitor of TRPM3 channels
Patchliner publication in British Journal of Pharmacology (2008)
Authors:
Naylor J., Milligan C.J., Zeng F., Jones C., Beech D.J.