Begum, R;
Bakiri, Y;
Volynski, KE;
Kullmann, DM;
(2016)
Action potential broadening in a presynaptic channelopathy.
Nature Communications
, 7
, Article 12102. 10.1038/ncomms12102.
Preview |
Text
ncomms12102.pdf Download (1MB) | Preview |
Abstract
Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.
| Type: | Article |
|---|---|
| Title: | Action potential broadening in a presynaptic channelopathy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms12102 |
| Publisher version: | http://dx.doi.org/10.1038/ncomms12102 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, EPISODIC ATAXIA TYPE-1, MOSSY FIBER BOUTONS, CEREBELLAR PURKINJE-CELLS, AXON INITIAL SEGMENT, CA2+-ACTIVATED K+ CHANNELS, POTASSIUM CHANNELS, CA2+ CHANNELS, TRANSMITTER RELEASE, NERVE-TERMINALS, P/Q-TYPE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1504409 |
Archive Staff Only
 |
View Item |
