Involvement of Kv1 Potassium Channels in Spreading Acidification and Depression in the Cerebellar Cortex
| Autor: | Wangcai Gao, Kenneth C. Reinert, Gang Chen, Claudia M. Hendrix, Timothy J. Ebner, Laurentiu S. Popa, M. Elizabeth Ross |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Baclofen Potassium Channels Time Factors Physiology GABA Antagonists Mice chemistry.chemical_compound Cyclin D2 Drug Interactions Cerebral Cortex Chemistry General Neuroscience Cortical Spreading Depression Glutamate receptor Potassium channel Carbamazepine medicine.anatomical_structure Neutral Red Cerebellar cortex Knockout mouse Anticonvulsants Female medicine.symptom Diagnostic Imaging Ataxia Glutamic Acid Scorpion Venoms Mice Transgenic Parallel fiber Bicuculline behavioral disciplines and activities Tityustoxin Cyclins mental disorders Potassium Channel Blockers Reaction Time medicine Animals Episodic ataxia Dose-Response Relationship Drug Dose-Response Relationship Radiation medicine.disease Electric Stimulation Acetazolamide Mice Inbred C57BL Shaker Superfamily of Potassium Channels Peptides Acids Neuroscience |
| Zdroj: | Journal of Neurophysiology. 94:1287-1298 |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.00224.2005 |
| Popis: | Spreading acidification and depression (SAD) is a form of propagated activity in the cerebellar cortex characterized by acidification and a transient depression in excitability. This study investigated the role of Kv1 potassium channels in SAD using neutral red, flavoprotein autofluorescence, and voltage-sensitive dye optical imaging in the mouse cerebellar cortex, in vivo. The probability of evoking SAD was greatly increased by blocking Kv1.1 as well as Kv1.2 potassium channels by their specific blockers dendrotoxin K (DTX-K) and tityustoxin (TsTX), respectively. DTX-K not only greatly lowered the threshold for evoking SAD but also resulted in multiple cycles of spread and spontaneous SAD. The occurrence of spontaneous SAD originating from spontaneous parallel fiber-like beams of activity suggests that blocking Kv1 channels increased parallel fiber excitability. This was confirmed by the generation of parallel fiber-like beams with the microinjection of glutamate into the upper molecular layer in the presence of DTX-K. The dramatic effects of DTX-K suggest a possible connection between SAD and episodic ataxia type 1 (EA1), a Kv1.1 potassium channelopathy. The threshold for evoking SAD was significantly lowered in the Kv1.1 heterozygous knockout mouse compared with wild-type littermates. Carbamazepine and acetazolamide, both effective in the treatment of EA1, significantly decreased the likelihood of evoking SAD. Blocking GABAergic neurotransmission did not alter the effectiveness of DTX-K. The cyclin D2 null mouse, which lacks cerebellar stellate cells, also exhibited SAD. Therefore blocking Kv1 potassium channels establishes the conditions needed to generate SAD. Furthermore, the results are consistent with the hypothesis that SAD may underlie the transient attacks of ataxia characterizing EA1. |
| Databáze: | OpenAIRE |
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