The limitation of the Purkinje cells’ impulse activity in the laboratory mice's cerebellum by in vivo activation of SK channels

Polina A. Egorova , Olga L. Vlasova , Ilya B. Bezprozvanny
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Abstract

This study tested the effect of intravenous injections of CyPPA [the activator of small conductance calcium-activated potassium channels of types 2 and 3 (SK2/SK3)] on the firing frequency of cerebellar Purkinje cells of laboratory male mice at the age of 6 months via the method of extracellular in vivo recordings from Purkinje cells. This method revealed that 1 mM CyPPA tail vein injections lead to progressive reduction of Purkinje cells firing frequency. Thus, simple spike's firing frequency decreases by 16% in one hour after injection, by 49% in two hours after injection, and by 61% in three hours. The obtained results confirmed the hypothesis about the important role of SK channels in the maintenance of Purkinje cells spontaneous activity in vivo. Since deterioration of biophysical and physiological functions is observed in many cerebellar ataxias, SK channels can serve as a potential target for the treatment of such disorders.

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体内活化SK通道对实验小鼠小脑浦肯野细胞冲动活动的限制
本研究通过细胞外在体记录浦肯野细胞的方法,检测了静脉注射CyPPA[2型和3型小电导钙活化钾通道激活剂(SK2/SK3)]对6月龄实验室雄性小鼠小脑浦肯野细胞放电频率的影响。结果表明,1 mM CyPPA尾静脉注射可使浦肯野细胞放电频率逐渐降低。因此,注射后1小时内,简单脉冲的发射频率下降了16%,注射后2小时下降了49%,注射后3小时下降了61%。这些结果证实了SK通道在体内维持浦肯野细胞自发活性中的重要作用。由于在许多小脑共济失调中观察到生物物理和生理功能的恶化,SK通道可以作为治疗此类疾病的潜在靶点。
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