RT - Journal Article T1 - Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia JF - BCN YR - 2016 JO - BCN VO - 7 IS - 1 UR - http://bcn.iums.ac.ir/article-1-573-en.html SP - 57 EP - 62 K1 - Cerebellar ataxia K1 - Smallconductance calciumactivated potassium channels K1 - Deep cerebellar nuclei K1 - Computer simulation AB - Introduction: Loss of inhibitory output from Purkinje cells leads to hyperexcitability of the Deep Cerebellar Nuclei (DCN), which results in cerebellar ataxia. Also, inhibition of small-conductancecalcium-activated potassium (SK) channel increases firing rate  f DCN, which could cause cerebellar ataxia. Therefore, SK channel activators can be effective in reducing the symptoms of this disease, and used for the treatment of cerebellar ataxia. In this regard, we hypothesized that blockade of SK channels in different compartments of DCN would increase firing rate with different value. The location of these channels has different effects on increasing firing rate.  Methods: In this study, multi-compartment computational model of DCN was used. This computational stimulation allowed us to study the changes in the firing activity of DCN neuron without concerns about interfering parameters in the experiment. Results: The simulation results demonstrated that blockade of somatic and dendritic SK channel increased the firing rate of DCN. In addition, after hyperpolarization (AHP) amplitude increased with blocking SK channel, and its regularity and resting potential changed. However, action potentials amplitude and duration had no significant changes. The simulation results illustrated a more significant contribution of SK channels on the dendritic tree to the DCN firing rate. SK channels in the proximal dendrites have more impact on firing rate compared to distal dendrites. Discussion: Therefore, inhibition of SK channel in DCN can cause cerebellar ataxia, and SK channel openers can have a therapeutic effect on cerebellar ataxia. In addition, the location of SK channels could be important in therapeutic goals. Dendritic SK channels can be a more effective target compared to somatic SK channels LA eng UL http://bcn.iums.ac.ir/article-1-573-en.html M3 ER -