Table 1.
The pathophysiological and physiological effects of TRPC knockouts and knockdowns.
| Type | Effects | Authors | Reference |
|---|---|---|---|
| TRPC1 KO | TRPC1 KO mice exhibited increased mGluR agonist-induced non-selective inward currents in the CA1 neurons of the hippocampus | Kepura et al., 2020 | [287] |
| TRPC1 KO mice did not develop pulmonary hypertension under chronic hypoxia and had reduced vascular remodeling; however, right ventricular hypertrophy was similar to that in WT mice | Malczyk et al., 2013 | [163] | |
| TRPC1 KO mice showed impairment in spatial working memory and fear memory formation but innate fear behavior was unaffected; activation of mGluR increased inward currents in hippocampal neurons from WT but not from TRPC KO mice | Lepannetier et al., 2018 | [223] | |
| TRPC1 KO mice fed a high fat diet exhibited reduced fat mass, fasting glucose concentrations, and autophagy markers, whereas apoptosis markers were increased | Krout et al., 2017 | [200] | |
| Tamoxifen-inducible TRPC1 genetic ablation in the hippocampus impaired mGluR-induced ERK1/2 activation, diminished mGluR-LTD, and decreased memory extinction | Yerna et al., 2020 | [224] | |
| TRPC1 KO mice exhibited increased cerebral ischemia/reperfusion-induced infarction, neurological severity score, memory impairment, and oxidative stress. | Xu et al., 2018 | [231] | |
| TRPC1 KO mice exhibited a reduced airway remodeling following house dust mite challenge with decreases in mucus production, cytokine secretion, and collagen deposition. | Pu et al., 2019 | [286] | |
| TRPC1 KO mice exhibited no deficit of learning and memory under physiological conditions, but exacerbated learning and memory deficits induced by amyloid-β (Aβ), associated with Alzheimer’s disease | Li et al., 2018 | [210] | |
| TRPC1 KO mice exhibited a reduced endothelial progenitor cell function secondary to calmodulin/endothelial nitric oxide synthase downregulation | Du et al., 2018 | [167] | |
| Improved motor performance and an increased density of striatal medium spiny neuron spines in a mouse model of Huntington disease | Wu et al., 2018 | [222] | |
| TRPC3 KO | TRPC3 KO mice exhibited ameliorated hypertension through reduction of angiotensin II-induced mitochondrial ROS generation | Wang et al., 2017 | [159] |
| TRPC3 KO impaired the pluripotency of undifferentiated mouse embryonic stem cells and repressed their neural differentiation | Hao et al., 2018 | [215] | |
| TRPC3 KO mice exhibited reduced pilocarpine-induced seizures and theta activity involved in status epilepticus | Phelan et al., 2017 | [237] | |
| Phenylephrine-induced vasoconstriction and endothelium-dependent acetylcholine-induced vasodilation were reduced in TRPC3 KO mouse mesenteric arteries, whereas KCl- or pressure-induced vasoconstriction was unaltered. | Yeon et al., 2014 | [170] | |
| Increase of mGluR1-induced slow EPSC by GABABR activation was absent in TRPC3 KO mouse cerebellar Purkinje neurons but unaltered in TRPC1, TRPC4 and TRPC1/4/5/6 KO Purkinje neurons | Tian & Zhu, 2018 | [234] | |
| TRPC3 KO mice exhibited a delayed occurrence of inflammation-induced preterm labor | Jing et al., 2018 | [251] | |
| TRPC3 KD | TRPC3 KD resulted in a decreased insulin-mediated glucose uptake in adult skeletal muscle cells | Lanner et al., 2009 | [203] |
| TRPC3 KD resulted in a reduced angiotensin II-induced Ca2+ influx in VSMC from spontaneously hypertensive rats | Liu et al., 2009 | [157] | |
| TRPC4 KO | TRPC4 KO mice exhibited a reduced self-administration of cocaine, but normal learning for natural reward | Klipec et al., 2016 | [226] |
| TRPC4 KO mice lack store-operated Ca2+ currents and agonist-dependent vasorelaxation | Freichel et al., 2001 | [165] | |
| TRPC5 KO | Compared with WT mice, TRPC5 KO mice had a reduced phosphatidylserine externalization and less apoptosis of cerebral neurons following ischemia-reperfusion | Guo et al., 2020 | [229] |
| Cortical neurons from TRPC5 KO mice were resistant to H2O2 toxicity as compared to WT neurons | Park et al., 2019 | [230] | |
| Acetylchoine-induced endothelium-dependent contractions were smaller in TRPC5 KO carotid arteries compared to WT mice; TRPC5 contributed by stimulating COX-2-mediatedprostanoid production from carotid artery endothelial cells | Liang et al., 2019 | [185] | |
| TRPC5 KO mice fed supplemental cholic acid had less liver enlargement than WT; hepatic bile acid was lower in TRPC5 KO mice | Alawi et al., 2017 | [283] | |
| TRPC5 KO mice demonstrated reduced nociceptive thresholds (thermal and mechanical) in a complete Freund’s adjuvant-induced unilateral arthritis model | Alawi et al., 2017 | [243] | |
| TRPC5 KO did not alter body temperature but was associated with increased accumulation of peritoneal leukocytes secreting inflammatory mediator in thioredoxin-treated LPS- injected mice. | Pereira et al., 2018 | [275] | |
| Isoliquiritigenin from Glycyrrhiza glabra (Licorice) inhibits atherosclerosis by blocking TRPC5 channel expression and lipid serum levels in an apolipoprotein E (ApoE) knockout mouse model and angiotensin II-stimulated vascular smooth muscle cells (VSMCs) | Qi et al., 2020 | [184] | |
| TRPC5 KO mice exhibited diminished innate fear levels in response to aversive stimuli and reduced response to metabotropic glutamate receptor activation in amygdala | Riccio et al., 2009 | [218] | |
| TRPC5 KD | Knockdown of TRPC5 increased chemosensitivity to temozolomide in glioblastoma | Zou et al., 2019 | [190] |
| TRPC6 KO | Compared to Akita mice, TRPC6 KO Akita mice exhibited increased insulin resistance, mesangial expansion, and glomerular injury but reduced albuminuria and tubular injury | Wang et al., 2019 | [202] |
| In the unilateral ureter obstruction model, TRPC6 knockout was linked to decreased expression of pro-fibrotic, with pro-inflammatory genes being unaffected | Kong et al., 2019 | [271] | |
| Reduces allergic airway response | Sel et al., 2008 | [284] | |
| Induction of hypoventilation resulted in severe arterial hypoxemia not found in wild type | Weissmann et al., 2006 | [161] | |
| Displayed reduced litter sizes and structural changes of the placenta | Hasna et al., 2019 | [252] | |
| Protects mice from mTBI-induced aortic endothelial dysfunction; | Chen et al., 2019 | [176] | |
| TRPC6 knockout has reno-protective effects in diabetic kidney disease, protecting the podocytes but not the glomerulus as a whole | Spires et al., 2018 | [205] | |
| In TRPC6 KO mice, pancreatic stellate cells (PSCs) exhibited decrease migration as compared to WT PSCs under hypoxic conditions | Nielsen et al., 2017 | [198] | |
| TRPC6 KO mice exhibited an elevated blood pressure and enhanced agonist-induced aortic contractility due to upregulation of constitutively active TRPC3-type channels | Dietrich et al., 2005 | [145] | |
| TRPC6 KD | Attenuated Ca2+ influx and the stress fiber formation induced by DHPG | Wang et al., 2019 | [269] |
| Prevented podocyte permeability increase induced by puromucin aminonucleaside | Sun et al., 2012 | [270] | |
| Increased autophagic flux and mitigated oxidative stress-induced apoptosis of proximal tubular cells | Hou et al., 2018 | [272] | |
| Decreased hypoxic increases of Ca2+ influx in PASMCs | Malczyk et al., 2017 | [162] | |
| Increased TGF-β1-induced Akt phosphorylation at Ser473 in VSMCs | Numaga-Tomita et al., 2019 | [154] | |
| Mitochondrial elongation, reduced phosphorylation of dynamin-related protein 1, and extracellular-signal-regulated kinase 1/2 | Ko et al., 2017 | [221] | |
| Unaltered ROS production, but increased inflammatory cytokines production compared to WT mice | Oda et al., 2017 | [288] | |
| TRPC6 KD | Increased density of striatal medium spiny neuron spines in a mouse model of Huntington disease | Wu et al., 2018 | [222] |
| TRPC1 or TRPC3 KD | Asthmatic mouse airway smooth muscle cells exhibited upregulated TRPC1 and TRPC3 and increased proliferation. Knockdown either of the channels reduced proliferation. | Zhang et al., 2018 | [285] |
| TRPC6 KO and TRPC5/6 DKO | TRPC6 KO mice and TRPC5/6 double KO mice were protected from H2O2-induced damage in a model of diabetic kidney disease | Ilatovskaya et al., 2018 | [206] |
| TRPC1/4 KO TRPC5 KO TRPC1 KO | LTP and pilocarpine-induced seizures are reduced in TRPC5 KO mice, but are unaltered in TRPC1/4 KO mice; mGluR-mediated epileptiform bursting in the hippocampal CA1 area is not affected in TRPC5 KO mice, but is abolished in TRPC1 KO and TRPC1/4 DKO mice; seizure-induced neural cell death in the hippocampus was reduced in both TRPC5 KO and TRPC1/4 DKO mice | Phelan et al., 2013 | [219] |
| TRPC1/4/5 KO | TRPC1/4/5 KO mice exhibited deficits in spatial working memory and relearning task, while spatial reference memory was not affected | Bröker-Lai et al., 2017 | [126] |
| TRPC1/4/5 KO mice exhibited decreased basal-evoked secretion, reduces readily releasable vesicles pool size, and accelerated synaptic depression during high-frequency stimulation, whereas TRPC5 KI showed short-term enhancement of synaptic strength during high frequency stimulation | Schwarz et al., 2019 | [225] | |
| TRPC3/6/7 KO | Compared to WT mice, triple TRPC3/6/7 KO mice had smaller infarct size when subjected to cerebral ischemia-reperfusion | Chen et al., 2017 | [228] |
| TRPC1/4/5/6 KO | Tetra-TRPC KO mice are protected from hyperglycemia-evoked vasoregression. In addition, the KO mice are resistant to the STZ-induced reduction in retinal layer thickness | Sachdeva et al., 2018 | [207] |
| TRPC1/4/5 or hepta-TRPC-KO | No change in persistent activity in entorhinal cortex neurons of layer V | Egorov et al., 2019 | [227] |
| Hepta- TRPC KO | Thapsigargin-induced store-operated Ca2+ entry was absent in Orai1 KO anterior pituitary cells, but was unaffected in hepta TRPC KO; conversely, spontaneous intracellular Ca2+ oscillations related to electrical activity was reduced in hepta TRPC1-7 KO mouse cells and unaffected in Orai1 KO mouse cells | Núñez et al., 2019 | [289] |