Neural extracellular potassium levels in response to retrodialysis insulin administration

Lecture Center 6

Insulin is widely used to treat both type 1 and type 2 diabetes, with a primary physiological role of blood glucose regulation: it is the first-choice treatment for a range of hyperglycemic conditions. One side-effect of insulin therapy is potential electrolyte imbalances in the blood, and specifically hypokalemia. Insulin acts to remove potassium from the bloodstream along with glucose. Work in our lab and others has shown that in addition to peripheral effects, insulin is a key regulator of central cognitive and metabolic processes, best-established within the hippocampus. Tight regulation of extracellular ion levels, including potassium concentration, is essential for optimal neuronal function; however, to date there have been no studies on potential ionic effects of insulin within the brain's extracellular space. In our research, we examined whether the hypokalemia that occurs in the periphery in response to exogenous insulin is also occurring in the central nervous system. We used hippocampal microdialysis in a rat model to address this question, which allowed us to administer exogenous insulin directly to the hippocampus at a controlled dosage and simultaneously take samples of the extracellular fluid to check potassium levels. Because insulin and glucose are important regulators of cognitive activity, likely to cause elevated neuronal firing and potentially affect potassium regulation, we examined the impact of insulin delivery both at baseline and during spontaneous alternation behavioral testing, a hippocampally dependent working memory task.