Modulation of volume-regulated anion channels by extra- and intracellular pH

We have studied the modulation of the volume-regulated anion channel (VRAC) in cultured endothelial cells from bovine pulmonary artery (CPAE cells) by extra- and intracellular pH. The patch-clamp technique was used in combination with a fluorimetric measurement of intracellular pH using BCECF. Swelling of CPAE cells was accompanied by a slow acidification. The metabolites lactate and HCO3- both permeate through VRAC. The inactivation of VRAC currents at positive potentials is accelerated at a decreased extracellular pH and decelerated at alkaline pH. The instantaneous current amplitude is only slightly affected. Intracellular alkalization reduced whereas acidification enhanced the currents flowing through VRAC at all potentials. HCO3- and lactate permeation, as well as the up-regulation of VRAC at an acidic intracellular pH might be related to a possible role of this channel in cellular pH regulation.