Biol. Pharm. Bull. 41(8)

1126 Biol. Pharm. Bull. 41, 1126 (2018) Vol. 41, No. 8 Current Topics Ion Channels as Therapeutic Targets for the Immune, Inflammatory, and Metabolic Disorders

Foreword Susumu Ohya Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University; Nagoya 467–8601, Japan.

A large number of ion channels and their auxiliary subunits osteoarthritis (OA). Recent ‘chondrocyte channelome’ studies play pivotal roles in various cellular signaling networks in have shown that a range of ion channels and transporters are nervous, cardiovascular, immune, metabolic, and endocrine expressed on plasma and intracellular membrane of chondro- systems. The ion channel dysfunctions produce “Channelo- cytes, and regulate multiple intracellular signaling pathways. pathies” such as neural, cardiovascular, immune, metabolic, The third review is “Physiological and Pathological Functions and endocrine disorders, therefore, ion channels are potential of Cl− Channels in Chondrocytes” by Yamamura et al. They therapeutic targets for treatment of their disorders. Review ar- first introduce the cation channels expressed in chondrocytes, ticles under the headings of ‘Ion Channels as Therapeutic Tar- and then review the physiological and pathophysiological roles gets for the Immune, Inflammatory, and Metabolic Disorders’ of Cl− channels/transporters composed of several superfami- will provide new insights and strategies to “Channelopathies.” lies (CFTR, ClC, TMEM16/ANO1). They play important roles Recent findings showed that voltage-gated calcium channels in control of the resting membrane potential, and are critical (VGCC) are responsible for the generation of inflammation to intracellular Ca2+ signaling. This review provides a novel and inflammatory pain. The first review is “Involvement of approach for ameliorating RA and OA severities. The forth Voltage-Gated Calcium Channels in Inflammation and Inflam- review is “Physiological and Pathophysiological Roles of Tran- matory Pain” by Sekiguchi et al. They especially focus on sient Receptor Potential Channels in Microglia-Related CNS the pathologic role of a T-type VGCC member, Cav3.2 as in Inflammatory Diseases” by Shirakawa and Kaneko. They in- colonic, bladder, and pancreatic pain with the related inflam- troduce the physiological and pathophysiological roles of TRP matory disorders (inflammatory bowel disease, cystitis, and Ca2+ channels (TRPC3, TRPV1,2,4, TRPM2, and TRPA1) in pancreatitis). Selective Cav3.2 blockers are effective in the the CNS inflammatory pathway, and review that microglial pre-clinical studies using animal models for neuropathic pain, TRP Ca2+ channels are attractive therapeutic targets for neu- and they may be also effective to the treatment of inflamma- rodegenerative diseases with CNS inflammation. The interme- 2+ 2+ + tory pain. Thermo-sensitive, transient receptor potential Ca diate-conductance Ca -activated K channel KCa3.1 contrib- channels (TRPs) play important roles in energy metabolism utes to the control of Ca2+ signaling in immune systems, and and adipogenesis by modulating thermogenesis in brown and regulates the expression and secretion of pro-inflammatory beige adipocytes. The second review is “Role of Thermo- cytokines and chemokines. KCa3.1 is an attractive therapeutic Sensitive Transient Receptor Potential Channels in Brown target for autoimmune, allergic, and inflammatory disorders. 2+ + Adipose Tissue” by Uchida et al. They first introduce the The last review is “Ca -Activated K Channel KCa3.1 as a pathological and physiological significance of thermo-sensitive Therapeutic Target for Immune Disorders” by Ohya and Kito. TRP channels subtypes. They review the emerging functions They introduce the recent advances in the post-transcriptional, of TRP channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM4, and post-translational and proteasomal regulations of KCa3.1 TRPM8, TRPC5, and TRPA1) in thermogenesis of brown and the roles of KCa3.1 in immune cell migration, cytokine and benign adipocytes, and discuss the therapeutic poten- productions, and phenotypic polarization. These reviews high- tials of TRP channels for preventing and combating obesity light current topics on the “Channelopathies” in immune, in- and related-metabolic disorders. Chondrocyte apoptosis and flammatory, and metabolic disorders, and provide great oppor- cartilage destruction result in rheumatoid arthritis (RA) and tunities for the future strategies in treatment of their disorders.