Differential activation of ATP-sensitive potassium channels during energy depletion in CA1 pyramidal cells and interneurones of rat hippocampus

Abstract

In the hippocampus, pyramidal cells are more vulnerable than granule cells and interneurones to energy depletion during hypoxia and ischaemia. The aim of the present study was to explore whether this difference is related to the lower expression of adenosine 5'-triphosphate-sensitive potassium (K_ATP) channels in pyramidal cells compared to other hippocampal neurones. Hippocampal slices were prepared from 10- to 13-day-old rats, and CA1 pyramidal cells and interneurones of the stratum radiatum were visually and electrophysiologically identified. Energy depletion was produced by removing glucose from the bath or by inhibiting mitochondrial metabolism using rotenone. In the perforated-patch configuration, both protocols elicited outward currents in only a minority of the pyramidal cells but in most of the interneurones. The currents started to develop 9–57 min after glucose deprivation and 4–16 min after rotenone application and reversed near the K⁺ equilibrium potential. Bath-applied diazoxide (0.3 mM), an opener of K_ATP channels, could activate additional currents. The sulphonylureas tolbutamide (0.5 mM) or glibenclamide (20 µM), two blockers of K_ATP channels, totally inhibited the currents induced by energy depletion and activated by diazoxide. The results demonstrate the differential activation of K_ATP channels during energy depletion in pyramidal cells and interneurones, and suggest that channel activation is neuroprotective against the deleterious effects of energy depletion.