Trpc5, human canonical transient receptor potential channel 5, is a Ca(2+)-permeable cation channel. It is predominantly expressed in the CNS, such as the hippocampus, cerebellum, etc., and also in peripheral tissues like the kidney and cardiovascular system. TRPC5 channels are activated by receptors coupled to Gq and phospholipase C and/or Gi proteins, and can gate in a store-dependent manner with partner proteins. They are involved in multiple Ca(2+)-related signaling pathways and are crucial for various biological functions from neurotransmission to cell migration and contractility [1].

Genetic models, especially Trpc5 knockout mice, have revealed its roles in multiple physiological and disease-related processes. For example, Trpc5-deficient mice show severely aggravated insulin-evoked hypoglycemia due to the lack of proper adrenaline rise in plasma, as TRPC5 in adrenal chromaffin cells is essential for the sympathetic counter-regulation to hypoglycemia [3]. Also, investigations using global and conditional deficient mice suggest the involvement of TRPC5 in metabolic diseases, energy balance, thermosensation, and pain-related conditions like osteoarthritis, rheumatoid arthritis, and inflammatory pain [2].

In conclusion, Trpc5 is a key ion channel in Ca(2+) signaling with diverse biological functions. Model-based research, especially using Trpc5 KO/CKO mouse models, has demonstrated its importance in diseases such as hypoglycemia-associated autonomic failure, metabolic diseases, and pain-related disorders, providing potential therapeutic targets for these conditions.

References:

1. Zholos, Alexander V. . TRPC5. In Handbook of experimental pharmacology, 222, 129-56. doi:10.1007/978-3-642-54215-2_6. https://pubmed.ncbi.nlm.nih.gov/24756705/

2. Khare, Pragyanshu, Chand, Jagdish, Ptakova, Alexandra, Vlachova, Viktorie, Zimmermann, Katharina. 2024. The TRPC5 receptor as pharmacological target for pain and metabolic disease. In Pharmacology & therapeutics, 263, 108727. doi:10.1016/j.pharmthera.2024.108727. https://pubmed.ncbi.nlm.nih.gov/39384022/

3. Bröker-Lai, Jenny, Rego Terol, José, Richter, Christin, Schwarz, Yvonne, Freichel, Marc. 2024. TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia. In The EMBO journal, 43, 5813-5836. doi:10.1038/s44318-024-00231-0. https://pubmed.ncbi.nlm.nih.gov/39375537/