The tandem pore domain K channel family mediates background K currents present in excitable cells. Currents passed by certain members of the family are enhanced by volatile anesthetics, thus suggesting a novel mechanism of anesthesia. The newest member of the family, termed TRESK (TWIK [tandem pore domain weak inward rectifying channel]-related spinal cord K channel), has not been studied for anesthetic sensitivity. We isolated the coding sequence for TRESK from human spinal cord RNA and functionally expressed it in Xenopus oocytes and transfected COS-7 cells. With both whole-cell voltage-clamp and patch-clamp recording, TRESK currents increased up to three-fold by clinical concentrations of isoflurane, halothane, sevoflurane, and desflurane. Nonanesthetics (nonimmobilizers) had no effect on TRESK. Various IV anesthetics, including etomidate, thiopental, and propofol, have a minimal effect on TRESK currents. Amide and ester local anesthetics inhibit TRESK in a concentration-dependent manner but at concentrations generally larger than those that inhibit other tandem pore domain K channels. We also determined that TRESK is found not only in spinal cord, but also in human brain RNA. These results identify TRESK as a target of volatile anesthetics and suggest a role for this background K channel in mediating the effects of inhaled anesthetics in the central nervous system.

Mouse and rat TRESK (TWIK-related spinal cord K+ channel) have different pharmacologic responses compared with human TRESK. In particular, we found stereospecific differences in response to isoflurane by the rodent TRESKs but not by human TRESK. TRESK may be a target site for the mechanism of action of volatile anesthetics.

At clinically achievable concentrations, methadone inhibits functional N-methyl-D-aspartate receptors. These results indicate a unique mode of action by this opioid that may enhance its ability to treat chronic pain and to limit opioid tolerance.

Purpose Deep anterior lamellar keratoplasty (DALK) is a challenging procedure that often results in conversion to penetrating keratoplasty (PKP). Preservation of Descemet’s membrane (DM) relies on indirect visualization of surgical planes. We describe a technique for enhanced visualization of key steps in DALK with intraoperative optical coherence tomography (iOCT). Methods Utilizing a microscope-mounted spectral-domain OCT system, high-resolution images of various steps. Results Specifically, images were obtained of trephination depth and proximity of the cannula tract to DM. Other key steps such as air cannula placement, assessment of DM position and integrity after attempted big bubble delivery, and assessment of graft-host apposition were readily visualized. Presence of intrastromal emphysema after air injection decreased visualization of deeper structures. Conclusion iOCT allows visualization of depth-dependent anatomy and changes from specific surgical interventions during DALK not appreciated with en face operating microscope view and has the potential to facilitate big bubble delivery.