Hydrogen sulfide induces Ca2+ release from intracellular Ca2+ stores and stimulates lactate production in spinal cord astrocytes

Abstract

Hydrogen sulfide (H₂S) is a well-known inhibitor of the mitochondrial electron transport chain (ETC). H₂S also increases intracellular Ca²⁺ levels in astrocytes, which are glial cells and that supply lactate as an energy substrate to neurons. Here, we examined the relationship between H₂S-induced metabolic changes and Ca²⁺ responses in spinal cord astrocytes. Na₂S (150 μM), an H₂S donor, increased the intracellular Ca²⁺ concentration, which was inhibited by an ETC inhibitor and an uncoupler of mitochondrial oxidative phosphorylation. Na₂S also increased the accumulation of extracellular lactate. Na₂S alone did not change intracellular ATP content, but decreased it when glycolysis was inhibited. The Na₂S-induced Ca²⁺ increase and accumulation of extracellular lactate were inhibited by emetine, an inhibitor of translocon complex, which mediates Ca²⁺ leak from the endoplasmic reticulum (ER). Furthermore, an inhibitor of the Ca²⁺-sensitive NADH shuttle decreased Na₂S-mediated accumulation of lactate. We conclude that inhibition of the mitochondrial ETC by H₂S induces Ca²⁺ release from mitochondria and the ER in spinal cord astrocytes, which increases lactate production. H₂S may promote glycolysis by activating the Ca²⁺-sensitive NADH shuttle and facilitating the supply of lactate from astrocytes to neurons.

Keywords: ATP; Astrocytes; Calcium; Hydrogen sulfide; Lactate.