Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia.
BACKGROUND
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-conductance calcium-activated potassium (SK) channel increases firing rate of 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.


CONCLUSIONS
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.
Computational Neuroscience Laboratory, Department of Biomedical Engineering, Faculty of Electrical Engineering, Sahand University of Technology, Tabriz, Iran.
Samira
S
Abbasi
Department of Mechatronics, School of Engineering Technologies, University of Tabriz, Tabriz, Iran.
Ataollah
A
Abbasi
Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Yashar
Y
Sarbaz
Computational Neuroscience Laboratory, Department of Biomedical Engineering, Faculty of Electrical Engineering, Sahand University of Technology, Tabriz, Iran.
Parviz
P
Shahabi
Cerebellar ataxia; Computer simulation; Deep cerebellar nuclei; Small-conductance calcium-activated potassium channels