Influence of metabolic disturbance on nervous function : clinical and experimental studies

University dissertation from Linköping : Linköpings universitet

Abstract: The present work consists of clinical and experimental studies and describes some effects of metabolic disturbance on nervous function. It is an electrophysiological examination of both single cells and patients exposed to metabolic insult or disease. The patch-clamp technique has been used for measurements of whole-cell currents in rat brain slices and studies of nerve conduction has been used as a clinical test on peripheral nervous function in young patients with insulin-dependent diabetes mellitus (IDDM).The objective of the clinical studies was to find out to what extent young IDDM patients with multiple insulin injection therapy (MIT) still develop peripheral nerve dysfunction and to elucidate the reason why.The objective of the experimental studies was to evaluate the effect of metabolic disturbance - induced chemically or by anoxia - on the membrane potential and the ionic conductances in hippocampal CA1 pyramidal cells.It is concluded that(1) despite MIT-treatment and good metabolic control nerve dysfunction is still common in an unselected group of children and adolescents with IDDM(2) the most important risk factors for nerve dysfunction in IDDM arc increased height and poor long-term metabolic control(3) metabolic inhibition at 22-24°C or anoxia at 33-34°C causes hyperpolarization and changes in the function of several types of K+ channels in CA1 pyramidal cells(4) a change in membrane potential by a few millivolts inhibited the spontaneous impulse firing(5) a transient opening of tolbutamide-sensitive K+ channels could explain the increase in grest and the hyperpolarization observed in most cells during metabolic inhibition(6) by this mechanism the excitablity decreases which may diminish the energy demand in cortical cells during different types of metabolic insult.

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