dampening of hyperexcitability in ca1 pyramidal neurons by polyunsaturated fatty acids acting on voltage-gated ion channels抑制多不饱和脂肪酸在ca1锥体神经元兴奋过度的电压门控离子通道.pdfVIP

Dampening of Hyperexcitability in CA1 Pyramidal Neurons by Polyunsaturated Fatty Acids Acting on Voltage-Gated Ion Channels 1,2 ¨ 3 1 3 ´ 1,2 Jenny Tigerholm *, Sara I. Borjesson , Linnea Lundberg , Fredrik Elinder , Erik Fransen 1 Department of Computational Biology, School of Computer Science and Communication, KTH Royal Institute of Technology, Stockholm, Sweden, 2 Stockholm Brain ¨ Institute, KTH Royal Institute of Technology, Stockholm, Sweden, 3 Division of Cell Biology, Department of Clinical and Experimental Medicine, Linkoping University, ¨ Linkoping, Sweden Abstract A ketogenic diet is an alternative treatment of epilepsy in infants. The diet, rich in fat and low in carbohydrates, elevates the level of polyunsaturated fatty acids (PUFAs) in plasma. These substances have therefore been suggested to contribute to the anticonvulsive effect of the diet. PUFAs modulate the properties of a range of ion channels, including K and Na channels, and it has been hypothesized that these changes may be part of a mechanistic explanation of the ketogenic diet. Using computational modelling, we here study how experimentally observed PUFA-induced changes of ion channel activity affect neuronal excitability in CA1, in particular responses to synaptic input of high synchronicity. The PUFA effects were studied in two pathological models of cellular hyperexcitability associated with epileptogenesis. We found that experimentally derived PUFA modulation of the A-type K (KA) channel, but not the delayed-rectifier