Voltage-gated potassium channels in multiple sclerosis: Overview and new implications for treatment of central nervous system inflammation and degeneration.
Inflammatory tissue damage and the presence of reactive immunocompetent T lymphocytes, macrophages, microglia, and dendritic cells (DCs) are characteristic features in the human chronic inflammatory demyelinating disease, multiple sclerosis (MS). Together, these cells orchestrate the inflammation and immunopathogenesis underlying the MS autoimmune disease processes and all up-regulate the same voltage-gated potassium (K(v)) channel, K(v)1.3, when fully activated. Only microglia, which mediate central nervous system (CNS) inflammatory processes (possibly playing a dual role of CNS protection and mediation of neuroinflammation/ neurodegeneration), and DC, which are pivotal to the induction of T cell responses, express the distinct K(v)1.5 prior to K(v)1.3 up-regulation. Although the precise functional roles of first K(v)1.5 and then K(v)1.3 channels are unclear, their differential expression is likely a common mechanism used by both microglia and DC, revealing K(v)1.5 (in addition to K(v)1.3) as a potentially important target for the development of new immunomodulatory therapies in MS.
Judge
Susan I V
SI
Department of Veterans Affairs (VA) Multiple Sclerosis Center of Excellence East, Baltimore, MD, USA. sjudge@umaryland.edu
Lee
Jennifer M
JM
Bever
Christopher T
CT
Hoffman
Paul M
PM
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy*; D009410:Nerve Degeneration / Q000517:prevention & control; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism*; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated