The involvement of K
3.1 in the TGF/Smad 2/3 signalling pathway. A diagrammatic representation of how Smad2/3 phosphorylation and subsequent nuclear translocation is reliant on an influx of extracellular Ca2+ and KCa3.1 ion channels. TGFβ1 stimulation triggers an influx of extracellular Ca2+, which in turns opens Ca2+-activated KCa3.1 K+ channels. KCa3.1 opening maintains a negative membrane which in turn promotes Ca2+ entry. Phosphorylation of Smad2/3 and therefore its downstream effects such as translocation and gene transcription are heavily reliant on Ca2+. KCa3.1 channel inhibition reduces Ca2+ entry, which in turn reduces Smad2/3 phosphorylation and nuclear translocation, and thus reduces TGFβ1-dependent gene transcription.