Enhancing Human Cutaneous Wound Healing through Targeted Suppression of Large Conductance Ca²⁺-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 Ba²⁺ was the exception and did not show similar effects. Single-channel recordings revealed that the Ba²⁺-insensitive large conductance Ca²⁺-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.