Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia
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 ata...
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| Format: | Article |
| Language: | English |
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Iran University of Medical Sciences
2016-01-01
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| Series: | Basic and Clinical Neuroscience |
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| Online Access: | http://bcn.iums.ac.ir/browse.php?a_code=A-10-188-1&slc_lang=en&sid=1 |
| _version_ | 1797284997912068096 |
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| author | Samira Abbasi Ataollah Abbasi Yashar Sarbaz Parviz Shahabi |
| author_facet | Samira Abbasi Ataollah Abbasi Yashar Sarbaz Parviz Shahabi |
| author_sort | Samira Abbasi |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-03-07T17:55:50Z |
| format | Article |
| id | doaj.art-719015f1b89d428d98da829893a10c72 |
| institution | Directory Open Access Journal |
| issn | 2008-126X 2228-7442 |
| language | English |
| last_indexed | 2024-03-07T17:55:50Z |
| publishDate | 2016-01-01 |
| publisher | Iran University of Medical Sciences |
| record_format | Article |
| series | Basic and Clinical Neuroscience |
| spelling | doaj.art-719015f1b89d428d98da829893a10c722024-03-02T12:14:08ZengIran University of Medical SciencesBasic and Clinical Neuroscience2008-126X2228-74422016-01-01715762Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar AtaxiaSamira Abbasi0Ataollah Abbasi1Yashar Sarbaz2Parviz Shahabi3 Computational Neuroscience Laboratory, Department of Biomedical engineering, Faculty of electrical engineering, Sahand University of Technology, Tabriz, Iran. Department of Mechatronics, School of Engineering Technologies, University of Tabriz, Tabriz, Iran. Assistant professor, School of Engineering- Emerging Technologies, University of Tabriz, Tabriz, Iran. Assistant professor, Neuroscience Research Center, Tabriz University of Medical Science, Tabriz, Iran. 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 channelshttp://bcn.iums.ac.ir/browse.php?a_code=A-10-188-1&slc_lang=en&sid=1Cerebellar ataxia Smallconductance calciumactivated potassium channels Deep cerebellar nuclei Computer simulation |
| spellingShingle | Samira Abbasi Ataollah Abbasi Yashar Sarbaz Parviz Shahabi Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia Basic and Clinical Neuroscience Cerebellar ataxia Smallconductance calciumactivated potassium channels Deep cerebellar nuclei Computer simulation |
| title | Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia |
| title_full | Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia |
| title_fullStr | Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia |
| title_full_unstemmed | Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia |
| title_short | Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia |
| title_sort | contribution of somatic and dendritic sk channels in the firing rate of deep cerebellar nuclei implication in cerebellar ataxia |
| topic | Cerebellar ataxia Smallconductance calciumactivated potassium channels Deep cerebellar nuclei Computer simulation |
| url | http://bcn.iums.ac.ir/browse.php?a_code=A-10-188-1&slc_lang=en&sid=1 |
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