At the level of skin wounds, an electrical potential difference develops between the edges of the wound and the center of the wound, which favors the migration of cells in the process of their healing. Cells migrate in an electric field because they have a certain electrical membrane potential. This potential is due to differences in the transmembrane electrochemical gradient. The transmembrane electrochemical gradient is due to the migration of sodium, potassium, and calcium ions into the corresponding ion channels. If this is the case, the modification of the functionality of these ion channels should influence the membrane potential and, as a consequence, the wound healing process. In this experiment, we set out to investigate whether the chemical manipulation of ion channels by amiodarone influences the wound healing process. Amiodarone blocks several types of ion channels, but at different concentrations: at low concentrations, it blocks only potassium channels; at medium concentrations, potassium and calcium channels; and at high concentrations, it blocks potassium, calcium, and sodium channels. We worked on rats that were given experimental skin lesions and evaluated the influence of the healing of these lesions upon the topical administration of amiodarone in three concentrations, 200 nM, 2000 nM and 200,000 nM, compared to an untreated group and a group treated with benzyl alcohol, the amiodarone solvent. In our experimental conditions, low concentration amiodarone promoted wound healing both in terms of duration of healing and also in terms of speed of healing. This means that blocking some ions, possibly potassium channels, might promote wound healing.

Wound healing involves physical, chemical and immunological processes. Transient receptor potential (TRP) and other ion channels are implicated in epidermal re-epithelization. Ion movement across ion channels can induce transmembrane potential that leads to transepithelial potential (TEP) changes. TEP is present in epidermis surrounding the lesion decreases and induces an endogenous direct current generating an epithelial electric field (EF) that could be implicated in wound re-epithelialization. TRP channels are involved in the activation of immune cells during mainly the inflammatory phase of wound healing. The aim of the study was to review the mechanisms of ion channel involvement in wound healing in in vivo experiments in murine (mice, rats) and how can this process be influenced. This review used the latest results published in scientific journals over the last year and this year to date (1 January 2023–31 December 3000) in order to include the in-press articles. Some types of TRP channels, such as TRPV1, TRPV3 and TRPA1, are expressed in immune cells and can be activated by inflammatory mediators. The most beneficial effects in wound healing are produced using agonists of TRPV1, TRPV4 and TRPA1 channels or by inhibiting with antagonists, antisense oligonucleotides or knocking down TRPV3 and TRPM8 channels.

Wound healing involves physical, chemical and immunological processes. Transient receptor potential (TRP) and other ion channels are implicated in epidermal re-epithelization. Ion movement across ion channels can induce transmembrane potential that leads to transepithelial potential (TEP) changes. TEP present in epidermis surrounding the lesion decreases and induces an endogenous direct current generating an epithelial electric field (EF) that could be implicated in wound re-epithelialization. TRP channels are involved in the activation of immune cells during the inflammatory phase of wound healing. The aim of the study was to review the mechanisms of ion channel involvement in wound healing in in vivo experiments in rodents (mice, rats, rabbits) and how can this process be influenced. This review used the latest results published in scientific journals over the last year and this year to date (1 January 2023–31 December 3000) in order to include the in-press articles. Some types of TRP channels, such as TRPV1, TRPV3, and TRPA1, are expressed in immune cells and can be activated by inflammatory mediators. The most beneficial effects in wound healing are produced using agonists of TRPV1, TRPV4 and TRPA1 channels or by inhibiting with antagonists, antisense oligonucleotides or knocking down TRPV3 and TRPM8 channels.

At the level of skin wounds, an electrical potential difference develops between the edges of the wound and the cen-ter of the wound, which favors the migration of cells in the process of their healing. Cells migrate in an electric field because they have a certain electrical membrane potential. This potential is due to differences in the trans-membrane electrochemical gradient. The transmembrane electrochemical gradient is due to the migration of sodium, potassium and calcium ions into the corresponding ion channels. If this is the case, the modification of the func-tionality of these ion channels should influence the membrane potential and, as a consequence, the wound healing process. In this experiment, we aimed to investigate to what extent amiodarone influences the wound healing pro-cess. Amiodarone blocks several types of ion channels but at different concentrations: at low concentrations it blocks only potassium channels, at medium concentrations potassium and calcium channels, and at high concentra-tions it blocks potassium, calcium and sodium channels. We worked on rats that were given experimental skin le-sions and evaluated the influence of the healing of these lesions upon the topical administration of amiodarone in 3 concentrations, 200nM, 2000nM and 200000nM, compared to an untreated group and a group treated with benzyl alcohol, the amiodarone solvent. In our experimental conditions, low concentration amiodarone promoted wound healing both in terms of duration of healing and also in terms of speed of healing. This means that blocking some ions, possibly potassium channels, might promote wound healing.

The migration of cells during the healing process is supported by an electrical potential difference that develops between the edges of skin wounds and the center of the wound. The electrical potential in cells' membranes is responsible for their migration in an electric field. The transmembrane electrochemical gradient differences cause this potential., Concomitant blockade of potassium and calcium channels by amiodarone at a medium dosage favored wound healing [1,2], but the effect was less intense than in the case of selective blocking of potassium channels. This suggested that blocking calcium channels partially antagonizes the effect of blocking potassium channels [8,9]. Since nimodipine blocks both L-type and T-type calcium channels, we decided to study which of these calcium channels are involved in wound healing. Hence, we performed an experimental study in which nimodipine was used in 3 concentrations: 200nM, which block only L-type calcium channels, 1000nM that block both L-type and T-type calcium channels and 10,000 nM, respectively, that block calcium channels and activate CB1 cannabinoid receptors. Blocking of calcium channels favored wound healing under our experimental conditions, but this happened only by simultaneously blocking of the L-type and T-type calcium channels, because only the medium nimodipine concentration had a statistically significant effect.

The healing process involves cell migration, which is sustained by an electrical potential difference that emerges between the edges of skin wounds and the center of the wound. The electrical potential in cells’ membranes is responsible for their migration in an electric field. The differences in the transmembrane electrochemical gradient generate this potential. The concomitant blockade of potassium and calcium channels by amiodarone at a medium dosage favored wound healing, but the effect was less intense than in the case of the selective blocking of potassium channels. According to this suggestion, blocking calcium channels might have a partial effect on blocking potassium channels. Given that nimodipine inhibits both L-type and T-type calcium channels, we aimed to investigate which of these calcium channels are involved in wound healing. Hence, we performed an experimental study in which nimodipine was used in three concentrations: 200 nM, which blocks only L-type calcium channels, 1000 nM, which blocks both L-type and T-type calcium channels, and 10,000 nM, which blocks calcium channels and activates CB1 cannabinoid receptors, respectively. The present research is a continuation of previous studies conducted by us, aimed to propose new perspectives on wound treatment. In conclusion, the blocking of calcium channels favored wound healing under our experimental conditions, but this happened only by simultaneously blocking the L-type and T-type calcium channels, because only the medium nimodipine concentration had a statistically significant effect.