The K+ channels KCa3.1 and Kv1.3 as novel targets for asthma therapy

Authors


Professor Peter Bradding, Department of Respiratory Medicine, Glenfield Hospital, Groby Rd, Leicester LE3 9QP, UK. E-mail: pbradding@hotmail.com

Abstract

Asthma affects 10% of the UK population and is an important cause of morbidity and mortality at all ages. Current treatments are either ineffective or carry unacceptable side effects for a number of patients; in consequence, development of new approaches to therapy are important. Ion channels are emerging as attractive therapeutic targets in a variety of non-excitable cells. Ion channels conducting K+ modulate the activity of several structural and inflammatory cells which play important roles in the pathophysiology of asthma. Two channels of particular interest are the voltage-gated K+ channel Kv1.3 and the intermediate conductance Ca2+-activated K+ channel KCa3.1 (also known as IKCa1 or SK4). Kv1.3 is expressed in IFNγ-producing T cells while KCa3.1 is expressed in T cells, mast cells, macrophages, airway smooth muscle cells, fibroblasts and epithelial cells. Both channels play important roles in cell activation, migration, and proliferation through the regulation of membrane potential and calcium signalling. We hypothesize that KCa3.1- and/or Kv1.3-dependent cell processes are one of the common denominators in asthma pathophysiology. If true, these channels might serve as novel targets for the treatment of asthma. Emerging evidence lends support to this hypothesis. Further validation through the study of the role that these channels play in normal and asthmatic airway cell (patho)physiology and in vivo models will provide further justification for the assessment of small molecule blockers of Kv1.3 and KCa3.1 in the treatment of asthma.

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