Table 1.
The involvement in cellular functions of the various TRP channels outlined in the review
| Function | Channel | Cellular action | Tissue | Reference |
|---|---|---|---|---|
| Cell death | TRPM2 | TRPM2-antisense oligonucleotide suppressed the H2O2/TNF-α-induced Ca2+ elevation and cell death. BAPTA prevented cell death induced by H2O2. |
Rat insulinoma β-cell line RIN-5F Monocyte cell line U937 |
(Hara et al., 2002) |
| TRPM2-siRNA suppressed the H2O2 -induces Ca2+ elevation and cell death. | Rat cultured cortical neurons | (Kaneko et al., 2006) | ||
| TRPM2-S, a dominant negative isoforms of TRPM2, inhibited the H2O2 and Amyloid β-peptide-induces Ca2+ elevation and cell death. PARP inhibitors attenuated H2O2 induced cell death. |
Rat cultured striatal cells | (Fonfria et al., 2005) | ||
| Cell death induced by H2O2 was shown to be mediated both by plasma membrane localized TRPM2 and lysosomal localized TRPM2 channels. | Rat insulinoma β-cell line INS-1 | (Lange et al., 2009) | ||
| H2O2 Increased PARP/procaspases -8, -9, -7, and -3 cleavage. BAPTA blocked cell death induced by TRPM2 activation. |
Human monocytic U937-ecoR cells | (Zhang et al., 2006) | ||
| TRPM7 | Prolonged OGD elicited ROS production which induced TRPM7 activation and cell death. Suppressing TRPM7 expression with siRNA prevented Ca2+ entry, ROS production and cell death. |
Cultured cortical neurons | (Aarts et al., 2003) | |
| Suppression of TRPM7 expression decreased delayed neuronal death following transient global cereberal ischemia. | Rat hippocampal neurons (in vivo) | (Sun et al., 2009) | ||
| Drosophila TRP | Cells expressing constitutively active mutant channel (trpP365) display severe degeneration. | Drosophila photoreceptor cells (in vivo) | (Yoon et al., 2000) | |
| TRPC1 | Overexpression of TRPC1 inhibited NFκB activity and increased susceptibility to apoptosis, induced by TNF-α together with cyclohexamide or staurosporine. TRPC1-siRNA treatment prevented the increased in susceptibility to apoptosis. | IEC-6 intestinal epithelial cells | (Marasa et al., 2006) | |
| TRPC3 | High level of apoptosis was observed in response to ischemia- reperfusion treatment in cells overexpressing TRPC3. | Cultured mice cardiomyocytes | (Shan et al., 2008) | |
| TRPC7 | Increased intracellular Ca2+ and basal & angiotensin II-induced- apoptosis was observed in cells overexpressing TRPC7. | Cultured neonatal rat cardiomyocytes | (Satoh et al., 2007) | |
| Differentiation | TRPC1 | TRPC1 expression was significantly upregulated during myogenesis. | Murine C2C12 skeletal myoblasts | (Formigli et al., 2009) |
| TRPC1-siRNA treatment decreased calcium induced differentiation. | Human gingival keratinocytes | (Cai et al., 2006) | ||
| TRPC1 & TRPC3 | Increased TRPC1 and TRPC3 expression was observed under differentiating conditions. TRPC1 or TRPC3-siRNA treatment inhibited SOCE and differentiation. | Hippocampal cells H19-7 | (Wu et al., 2004) | |
| TRPC1 & TRPC4 | TRPC1/TRPC4-siRNA treatment prevented calcium induced differentiation. | Human keratinocyte cell line HaCaT | (Beck et al., 2008) | |
| TRPV4 | mRNA levels of TRPV4 was increased in correlation with osteoclast maturation. TRPV4 was found to be responsible for the sustained Ca2+ influx, which is necessary for terminal differentiation of osteoclast. | Cultured osteoclasts isolated from TRPV4−/− or control mice | (Masuyama et al., 2008) | |
| TRPV4 induced increased activation of the SOX9 (essential transcription factor for chondrocytes differentiation) promoter. | Murine chondrogenic cell line, ATDC5 | (Muramatsu et al., 2007). | ||
| TRPV6 | Increased TRPV6 expression was observed upon induction of differentiation. TRPV6-siRNA treated cells showed decreased expression of specific-differentiation markers. | Human primary keratinocytes | (Lehen’kyi et al., 2007a) | |
| Proliferation | TRPC1 | These cells showed increased TRPC1 expression and enhanced proliferation. | Keratinocyte from Darier’s disease patients | (Pani et al., 2006) |
| Antisense knock-down of TRPC1 protein led to decreased bFGF- mediated Ca2+ influx and proliferation. | Embryonic rat neural stem cells | (Fiorio et al., 2005) | ||
| TRPC1-siRNA treatment inhibited platelet-derived growth factor- induced proliferation. | Human osteoblastic cells MG-63 Murine osteoblast cell line MC3T3 |
(Abed et al., 2009) | ||
| Proliferative cells showed upregulation in TRPC1 expression. TRPC1- antisense oligonucleotide suppressed the SOC current and decreased cell growth rate. | Primary cultured PASMC | (Golovina et al., 2001; Sweeney et al., 2002) | ||
| Overexpression of caveolin-1 prevented TRPC1-induced proliferation and overexpression of STIM1 enhanced the proliferation. | Human submandibular gland cells | (Pani et al., 2009) | ||
| TRPC1 & TRPC4 | TRPC1 and TRPC4 shRNA inhibited neurite extention. | Human embryonic stem cells | (Weick et al., 2009) | |
| TRPC4 | TRPC4-siRNA attenuated ATP-induced proliferation. Nonphosphorylatable CREB mutant prevented both the increased TRPC4 expression and proliferation. | Primary cultured PASMC | (Zhang et al., 2004) | |
| TRPC6 | PDGF induced an increase in TRPC6 expression, SOC current and proliferation. c-jun downregulation attenuated the increased TRPC6 expression. TRPC6 - antisense oligonucleotides reduced SOC current and PDGF-mediated proliferation. | Primary cultured PASMC | (Yu et al., 2003) | |
| TRPC6-siRNA attenuated proliferation. | PASMCs from patients with idiopathic pulmonary arterial hypertension | (Yu et al., 2004). | ||
| Overexpression of TRPC6 resulted in an increase of cell proliferation rate while knockdown of TRPC6 expression had the opposite effect. | Human hepatoma cell lines Huh- 7 and HepG2 | (El et al., 2008) | ||
| Stimulation of the α1-AR resulted in increased proliferation together with increased TRPC6 and CDK4 expression, NFAT activation and decreased p27 expression. TRPC6 antisense nucleotide inhibited proliferation. | Primary human prostate cancer epithelial cells | (Thebault et al., 2006) | ||
| Hypoxia treatment induced aggressive growth, activation of the Notch signaling, increased TRPC6 expression, intracellular Ca2+ and NFAT activation. TRPC6-siRNA prevented the aggressive glioma growth and invasion, Ca2+ elevation and NFAT activation. | Primary cells and cell lines derived from glioblastoma multiforme | (Chigurupati et al., 2010) | ||
| Mice expressing activated calcineurin displayed heart hypertrophy and elevated TRPC6 expression. Overexpression of TRPC6 in transgenic mice induced NFAT activation. | Mice cardiomyocytes (in vivo) | (Kuwahara et al., 2006) | ||
| Inhibition of TRPC6 activity by the dominant negative isoform, DNC6, inhibited cell proliferation. TRPC6 was found to be required for tumor growth in vivo. | Gastric cancer cells AGS and MKN45 in vivo experiment in nude mice |
(Cai et al., 2009) | ||
| inhibition of TRPC6 activity by the dominant negative isoform, DNC6, inhibits VEGF induced proliferation. | Human umbilical vein endothelial cells | (Ge et al., 2009) | ||
| TRPM7 | TRPM7-siRNA suppressed the angiotensin II-induced-elevation in intracellular Mg2+ concentration, and cell growth. | Vascular smooth muscle cells | (He et al., 2005) | |
| TRPM7-siRNA treatment inhibited both basal and platelet-derived growth factor-induced proliferation | Human osteoblastic cells MG-63 Murine osteoblast cell line, MC3T3 |
(Abed et al., 2009) | ||
| TRPM7-siRNA reduced cell proliferation via an inhibition of the G1 to S phase transition in the cell cycle. | Retinoblastoma cells | (Hanano et al., 2004) | ||
| TRPM8 | Higher transcript levels of TRPM8 was observed in malignant relative to non-malignant tissues, with correlation to tumor stages | Human primary prostate carcinoma | (Fuessel et al., 2003) | |
| TRPV6 | TRPV6 was up-regulated in prostate cancer, in correlation with the tumor grade and aggressiveness. | Human prostate tissue | (Fixemer et al., 2003; Wissenbach et al., 2001) | |
| TRPV6-siRNA inhibited cell proliferation rate. | Human prostate cancer cell line, LNCaP | (Lehen’kyi et al., 2007b) | ||
| Elevated TRPV6 level was observed in prostate, breast, thyroid, colon, and ovarian carcinomas, in comparison with normal tissues. | (Zhuang et al., 2002) | |||
| Transmitter release | TRPM7 | TRPM7 is localized to the synaptic vesicles and interacts with snapsin, synapsin I and synaptotagmin. The amplitudes, quantal sizes, and decay times of the EPSPs correlated with TRPM7 expression levels. Dominant-negative TRPM7 mutant suppressed the postsynaptic responses. TRPM7 specific siRNA inhibited vesicles fusion. |
Primary rat superior cervical ganglion neurons PC12 |
(Krapivinsky et al., 2006) (Brauchi et al., 2008) |