Chronic hyperglycaemia increases neuronal sensitivity to high potassium in hippocampal slices from streptozotocin-treated diabetic rats

The chronic hyperglycaemia associated with diabetes mellitus increases susceptibility to epileptiform-like activity in the central nervous system. Changes in extracellular potassium levels directly influence neuronal excitability and significantly one of the major regulators of extracellular potassium, the Na-K ATPase, is known to be down-regulated by chronic hyperglycaemia. The sensitivity of hippocampal slices, from rats made diabetic for 2-3 weeks with streptozotocin, to increases in the extracellular potassium concentration ([K+](o)) was, therefore, investigated. Raising [K+](o) to 10 mM increased the number of orthodromically-evoked population spikes (PSs) in area CA1. This recruitment was significantly greater in hippocampal slices from diabetic rats, which also exhibited significantly more spontaneous activity. These findings confirm a diabetes-dependent increase in sensitivity of central neurones to changes in [K+](o) and may help to explain the increased susceptibility to epileptiform activity in this disease state. (C) 2000 Elsevier Science Ireland Ltd. Ail rights reserved.