MODULATION OF LOCUS-COERULEUS NEURONS BY EXTRACELLULAR AND INTRACELLULAR ADENOSINE 5'-TRIPHOSPHATE

The cell membrane of rat locus coeruleus (LC) neurons is sensitive to both extra- and intracellular ATP. Extracellular ATP or its enzymatically stable analogues activate membrane receptors of the P-2 type. These receptors inhibit a persistent potassium current and simultaneously activate a nonselective cationic conductance. The resulting depolarization increases the spontaneous firing rate. A decrease in the concentration of intracellular ATP during hypoxia or hypoglycemia opens ATP-sensitive K+ (K-ATP) channels of LC neurons. The resulting hyperpolarization depresses the discharge of action potentials and conserves energy. The hypoxia-induced hyperpolarization is additionally due to the release of adenosine from neighboring neurons or glial cells. A certain class of compounds, termed potassium channel openers, also decrease the firing, while sulphonylurea antidiabetics known to block K-ATP channels increase it. Sulphonylurea antidiabetics antagonize the excitability decrease induced both by potassium channel openers and metabolic damage.