Background
Ryanodine receptors are calcium channels mediating calcium-induced calcium release. It is known that ryanodine receptors influence keratinocyte differentiation and barrier homeostasis. Our goal was to examine the in vivo role of ryanodine receptors in the healing of full-thickness dermal wounds.

Materials and Methods
The experiments were performed on 60 male SKH-1 hairless mice using skin fold chambers in the dorsal region. A standardized (4 mm diameter) circular wound was made on one side of the skin fold. Photographs were taken for the determination of wound closure rate during the 20-days observation period. In control group 1 (n=20) the wound was treated with sterile saline, the animals in group 2 (n=20) received ryanodine receptor agonist 4-chloro-m-cresol topically (2.5 mM), while in group 3 (n=20) dantrolene, an antagonist of ryanodine receptors was applied topically (100uM). Different parameters of microcirculation were monitored by means of intravital videomicroscopy. Tissue biopsies were taken for routine histology after days 4, 12 and 20, respectively.

Result
Treatment with 4-chloro-m-cresol did not influence the studied parameters, but dantrolene accelerated the wound closure rate and improved both epidermal and dermal regeneration. The antagonism of ryanodine receptors increased the vessel diameters during the process of healing and increased the blood flow in the capillaries at all times of measurement. Moreover, application of dantrolene decreased leukocyte-endothelial cell interactions during the inflammatory phase.

Conclusion
Inhibition of ryanodine receptor-mediated effects positively influences skin healing. Thus, dantrolene may be of therapeutic potential in the treatment of wounds.
The study was supported by TAMOP-4.2.2.A-11/1/KONV-2012-0035.