Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

2019/11/23 by Katy M. Roach, Peter Bradding · 27 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis #Ion channel regulation and function #Cardiac electrophysiology and arrhythmias

paper · doi:10.1111/bph.14939

Abstract

The role of Ca 2+ signalling in fibroblasts is of great interest in fibrosis‐related diseases. Intracellular free Ca 2+ ([Ca 2+ ] i ) is a ubiquitous secondary messenger, regulating a number of cellular functions such as secretion, metabolism, differentiation, proliferation and contraction. The intermediate conductance Ca 2+ ‐activated K + channel K Ca 3.1 is pivotal in Ca 2+ signalling and plays a central role in fibroblast processes including cell activation, migration and proliferation through the regulation of cell membrane potential. Evidence from a number of approaches demonstrates that K Ca 3.1 plays an important role in the development of many fibrotic diseases, including idiopathic pulmonary, renal tubulointerstitial fibrosis and cardiovascular disease. The K Ca 3.1 selective blocker senicapoc was well tolerated in clinical trials for sickle cell disease, raising the possibility of rapid translation to the clinic for people suffering from pathological fibrosis. This review after analysing all the data, concludes that targeting K Ca 3.1 should be a high priority for human fibrotic disease.

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