Premium
Ca 2+ signalling in fibroblasts and the therapeutic potential of K Ca 3.1 channel blockers in fibrotic diseases
Author(s) -
Roach Katy M.,
Bradding Peter
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14939
Subject(s) - calcium signaling , intracellular , fibroblast , fibrosis , channel blocker , cell growth , endocrinology , medicine , cell , second messenger system , secretion , pharmacology , microbiology and biotechnology , chemistry , cancer research , biology , calcium , biochemistry , in vitro
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.