A Novel Mechanism of pH Buffering in C. elegans Glia: Bicarbonate Transport via the Voltage-Gated ClC Cl- Channel CLH-1.

An important function of glia is the maintenance of the ionic composition and pH of the synaptic microenvironment. In terms of pH regulation, HCO3- buffering has been shown to be important in both glia and neurons. Here, we used in vivo fluorescent pH imaging and RNA sequencing of the amphid sheath glia of Caenorhabditis elegans to reveal a novel mechanism of cellular HCO3- uptake. While the classical mechanism of HCO3- uptake involves Na+/HCO3- cotransporters, here we demonstrate that the C. elegans ClC Cl- channel CLH-1 is highly permeable to HCO3- and mediates HCO3- uptake into amphid sheath glia. CLH-1 has homology and electrophysiological properties similar to the mammalian ClC-2 Cl- channel. Our data suggest that, in addition to maintaining synaptic Cl- concentration, these channels may also be involved in maintenance of synaptic pH via HCO3- flux. These findings provide an exciting new facet of study regarding how pH is regulated in the brain.