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

TRPM3 PS C Dataicon pl   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

icon pl   Patchliner data and applications:PL TRPM3 
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).

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