Foreword

A large number of ion channels and their auxiliary subunits play pivotal roles in various cellular signaling networks in nervous, cardiovascular, immune, metabolic, and endocrine systems. The ion channel dysfunctions produce “Channelopathies” such as neural, cardiovascular, immune, metabolic, and endocrine disorders, therefore, ion channels are potential therapeutic targets for treatment of their disorders. Review articles under the headings of ‘Ion Channels as Therapeutic Targets for the Immune, Inflammatory, and Metabolic Disorders’ will provide new insights and strategies to “Channelopathies.”

Recent findings showed that voltage-gated calcium channels (VGCC) are responsible for the generation of inflammation and inflammatory pain. The first review is “Involvement of Voltage-Gated Calcium Channels in Inflammation and Inflammatory Pain” by Sekiguchi et al. They especially focus on the pathologic role of a T-type VGCC member, Cav3.2 as in colonic, bladder, and pancreatic pain with the related inflammatory disorders (inflammatory bowel disease, cystitis, and pancreatitis). Selective Cav3.2 blockers are effective in the pre-clinical studies using animal models for neuropathic pain, and they may be also effective to the treatment of inflammatory pain. Thermo-sensitive, transient receptor potential Ca²⁺ channels (TRPs) play important roles in energy metabolism and adipogenesis by modulating thermogenesis in brown and beige adipocytes. The second review is “Role of Thermo-Sensitive Transient Receptor Potential Channels in Brown Adipose Tissue” by Uchida et al. They first introduce the pathological and physiological significance of thermo-sensitive TRP channels subtypes. They review the emerging functions of TRP channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM4, TRPM8, TRPC5, and TRPA1) in thermogenesis of brown and benign adipocytes, and discuss the therapeutic potentials of TRP channels for preventing and combating obesity and related-metabolic disorders. Chondrocyte apoptosis and cartilage destruction result in rheumatoid arthritis (RA) and osteoarthritis (OA). Recent ‘chondrocyte channelome’ studies have shown that a range of ion channels and transporters are expressed on plasma and intracellular membrane of chondrocytes, and regulate multiple intracellular signaling pathways. The third review is “Physiological and Pathological Functions of Cl⁻ Channels in Chondrocytes” by Yamamura et al. They first introduce the cation channels expressed in chondrocytes, and then review the physiological and pathophysiological roles of Cl⁻ channels/transporters composed of several superfamilies (CFTR, ClC, TMEM16/ANO1). They play important roles in control of the resting membrane potential, and are critical to intracellular Ca²⁺ signaling. This review provides a novel approach for ameliorating RA and OA severities. The forth review is “Physiological and Pathophysiological Roles of Transient Receptor Potential Channels in Microglia-Related CNS Inflammatory Diseases” by Shirakawa and Kaneko. They introduce the physiological and pathophysiological roles of TRP Ca²⁺ channels (TRPC3, TRPV1,2,4, TRPM2, and TRPA1) in the CNS inflammatory pathway, and review that microglial TRP Ca²⁺ channels are attractive therapeutic targets for neurodegenerative diseases with CNS inflammation. The intermediate-conductance Ca²⁺-activated K⁺ channel K_Ca3.1 contributes to the control of Ca²⁺ signaling in immune systems, and regulates the expression and secretion of pro-inflammatory cytokines and chemokines. K_Ca3.1 is an attractive therapeutic target for autoimmune, allergic, and inflammatory disorders. The last review is “Ca²⁺-Activated K⁺ Channel K_Ca3.1 as a Therapeutic Target for Immune Disorders” by Ohya and Kito. They introduce the recent advances in the post-transcriptional, and post-translational and proteasomal regulations of K_Ca3.1 and the roles of K_Ca3.1 in immune cell migration, cytokine productions, and phenotypic polarization. These reviews highlight current topics on the “Channelopathies” in immune, inflammatory, and metabolic disorders, and provide great opportunities for the future strategies in treatment of their disorders.