Acceleration of Cutaneous Wound Healing by Suppression of Large Conductance Ca2+-Activated K+ Channels

Abstract

We reported previously that the activity of the large-conductance calciumactivated potassium channels (BK Ca channel) could be strongly potentiated by certain derivatives of benzofuroindole scaffold when treated from extracellular side of the membrane (Gormemis et al., 2005; Ha et al., 2006). In order to localize the receptor site on the BK Ca channel, we surveyed the effects of CTBIC, the most potent benzofuroindole compound, on various K þ channels. While the compound increase the activity of voltage-gated K þ channels, K V 1.5 and HERG, CTBIC did not affect the activity of inward rectifier K þ channel, Kir3.1, significantly. Intriguingly enough, the same compound greatly decreased the activity of SK2, a different subclass of Ca 2þ -activated K þ channel. In addition, the affinity of charybdotoxin, a peptide pore-blocker, was reduced by the co-treatment with CTBIC, whereas that of tetraethylammonium, a small pore-blocking quaternary ammonium, was not altered. Guided by these results, we performed mutagenesis studies on the outer vestibule of the BK Ca channel to localize the residues that affect the binding of CTBIC. We identified three residues in the loop that connects with the pore-forming region of the channel, which was strongly affected by alanine substitution. Our results suggest that the turret region of the BK Ca channel may play a critical role in the modulation of the channel activity and may thus represent a therapeutic target site of K þ channels.

Rational design of flexible microneedles coupled with CaO2@PDA-loaded nanofiber films for skin wound healing on diabetic rats

“…7c shows the mechanical strength of the as-fabricated microneedles was about 0.46 N per needle with displacement at 600 μm, indicating they had sufficient mechanical strength to penetrate the skin. 43,44 Wound healing in vivo…”