Enhancing Human Cutaneous Wound Healing through Targeted Suppression of Large Conductance Ca 2+ -Activated K + Channels.

The modulation of K + channels plays a crucial role in cell migration and proliferation, but the effect of K + channels on human cutaneous wound healing (CWH) remains underexplored. This study aimed to determine the necessity of modulating K + channel activity and expression for human CWH. The use of 25 mM KCl as a K + channel blocker markedly improved wound healing in vitro (in keratinocytes and fibroblasts) and in vivo (in rat and porcine models). K + channel blockers, such as quinine and tetraethylammonium, aided in vitro wound healing, while Ba 2+ was the exception and did not show similar effects. Single-channel recordings revealed that the Ba 2+ -insensitive large conductance Ca 2+ -activated K + (BK Ca ) channel was predominantly present in human keratinocytes. NS1619, an opener of the BK Ca channel, hindered wound healing processes like proliferation, migration, and filopodia formation. Conversely, charybdotoxin and iberiotoxin, which are BK Ca channel blockers, dramatically enhanced these processes. The downregulation of BK Ca also improved CWH, whereas its overexpression impeded these healing processes. These findings underscore the facilitative effect of BK Ca channel suppression on CWH, proposing BK Ca channels as potential molecular targets for enhancing human cutaneous wound healing.