Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases

Abstract

T lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes. Patch-clamp studies revealed that the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. Using selective channel inhibitors in experimental animal models, in vivo studies further revealed the clinically relevant relationship between the channel expression and the development of chronic respiratory diseases, in which chronic inflammation or the overstimulation of cellular immunity in the airways is responsible for the pathogenesis. In chronic respiratory diseases, such as chronic obstructive pulmonary disease, asthma, diffuse panbronchiolitis and cystic fibrosis, in addition to the supportive management for the symptoms, the anti-inflammatory effects of macrolide antibiotics were shown to be effective against the over-activation or proliferation of T lymphocytes. Recently, we provided physiological and pharmacological evidence that macrolide antibiotics, together with calcium channel blockers, HMG-CoA reductase inhibitors, and nonsteroidal anti-inflammatory drugs, effectively suppress the Kv1.3-channel currents in lymphocytes, and thus exert anti-inflammatory or immunomodulatory effects. In this review article, based on the findings obtained from recent in vivo and in vitro studies, we address the novel therapeutic implications of targeting the lymphocyte Kv1.3-channels for the treatment of chronic or acute respiratory diseases.

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

“…The Kv1.3 channel is expressed both by vascular smooth muscle cells, where it stimulates their proliferation and migration [ 121 , 122 ], and by lymphocytes, where it promotes proliferation and cytokine production [ 122 , 123 , 124 , 125 ]. Kan et al studied the role of the Kv1.3 channel in macrophages and in the pathogenesis of atherosclerosis [ 122 ].…”

Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction

“…Lymphocyte activation is closely associated with K + channels on the lymphocyte membrane. K + channels function in controlling membrane potential, regulating cell volume and activating lymphocytes (31,32); therefore, they have an important role in the process of lymphocyte immunity. The present study investigated the current characteristics of voltage-dependent K + channels (K v ) and Ca 2+ -activated K + channels (K Ca ) in Jurkat T cells.…”

Nonsteroidal Anti-Inflammatory Drugs Quickly Resolve Symptoms Associated with EBV-Induced Infectious Mononucleosis in Patients with Atopic Predispositions

“…Since T-lymphocytes predominantly express the channels in their membranes [ 40 , 41 ], such a mechanism may have largely contributed to the immunosuppressive properties of NSAIDs in the present cases. In this context, in addition to the use of immunomodulatory drugs or corticosteroids [ 42 , 43 ], the use of selective blockers for the channel may also be beneficial [ 39 , 44 , 45 ]. Such drugs would shorten the duration of the disease, if administered early.…”