Hydrogen sulfide activates heterologously expressed human CFTR in Xenopus oocytes (1181.16)

Abstract

Hydrogen sulfide (H2S) has recently been recognized as a cellular signaling molecule. Physiological responses to H2S are often attributed to its impact on various sodium, calcium and potassium channels. However, little is known about the influence of H2S on chloride channels. This study investigated the putative regulation of the chloride channel CFTR (cystic fibrosis transmembrane conductance regulator) by H2S.Human CFTR was heterologously expressed in Xenopus oocytes and its activity was measured by microelectrode recordings using the two‐electrode voltage‐clamp technique. CFTR expression was verified by the application of forskolin/IBMX which elicited a transmembrane current that was sensitive to the CFTR inhibitor CFTRinh‐172. The H2S‐forming salt Na2S (5‐300 µM) significantly increased transmembrane currents of CFTR‐expressing oocytes but had no effect on native oocytes. The effect of Na2S was dose dependent and blocked by CFTRinh‐172. The slow H2S‐releasing molecule GYY4137 also activated CFTR, although to a smaller extent compared to Na2S. The adenylate cyclase inhibitor MDL‐12330A significantly decreased the activation of CFTR by Na2S. These data indicate that H2S activates CFTR in Xenopus oocytes by the cAMP/adenylate cyclase pathway. In epithelia, an increased CFTR activity may correspond to a secretory response to H2S which may be endogenously produced by the epithelium or a H2S‐generating microflora.Grant Funding Source: Supported by the German Research Foundation (AL‐1453/1‐2).