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- Renhorn, Jakob,1981-Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten (author)
Conformational Changes during Potassium-Channel Gating
- BookEnglish2018
Publisher, publication year, extent ...
- Linköping :Linköping University Electronic Press,2018
- 69 s.
- electronicrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:liu-146967
- ISBN:9789176853382
- https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-146967URI
- https://doi.org/10.3384/diss.diva-146967DOI
Supplementary language notes
- Language:English
- Summary in:English
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- SwePubSwePub
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Series
- Linköping University Medical Dissertations,0345-0082 ;1614
Notes
- Voltage-gated ion channels have a paramount importance in many physiological processes such as cell-to-cell communication, action potential-propagation, and cell motility. Voltage-gated ion channels are characterized by their ability to sense membrane voltage and to greatly change channel activity in response to small changes in the voltage. The ability to sense voltage resides in the four voltage-sensor domains (VSDs) surrounding the central ion-conducting pore. Membrane depolarization causes the inside of the membrane to become positively charged, electrostatically repelling the positively charged fourth transmembrane segment (S4), or voltage sensor, in the VSD, causing the voltage sensor to move outwards. This motion provides necessary energy to open the pore and allow ion conductivity. Prolonged channel activation leads to alterations in the selectivity filter which cease ion conductivity, in a process called slow inactivation. In this thesis, we investigated the movement of S4 during activation of the channel. We also studied the communication between the four subunits during activation as well as the communication between the pore domain and VSD during slow inactivation.We have shown that voltage sensors move approximately 12 Å outwards during activation. The positively charged amino acid residues in S4 create temporary salt bridges with negative counter-charges in the other segments of the VSD as it moves through a membrane. We have also shown that the movement of one of the four voltage sensors can affect the movement of the neighboring voltage sensors. When at least one voltage sensor has moved to an up-position, it stabilizes other voltage sensors in the up-position, increasing the energy required for the voltage sensor to return to the down position.We have also shown reciprocal communication between the pore domain and the VSDs. Alterations in the VSD or the interface between the pore and the VSD cause changes in the rate of slow inactivation. Likewise, modifications in the pore domain cause changes to the voltage-sensor movement. This indicates communication between the pore and the VSD during slow inactivation.The information from our work could be used to find new approaches when designing channel-modifying drugs for the treatment of diseases caused by increased neuronal excitability, such as chronic pain and epilepsy.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
- ion-channel
- electrophysiology
- neuron
- Jonkanal
- neurologi
- elektrofysiologi
- neuron
- aktionspotential
Added entries (persons, corporate bodies, meetings, titles ...)
- Elinder, Fredrik,Professor,1966-Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten(Swepub:liu)freel71 (thesis advisor)
- Engblom, David,Biträdande professor,1975-Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten(Swepub:liu)daven69 (thesis advisor)
- Pless, Stephan,Associate professorDepartment of drug design and pharmacology, University of Copenhagen, Denmark (opponent)
- Linköpings universitetAvdelning för neurobiologi (creator_code:org_t)
Internet link
- https://doi.org/10.3384/diss.diva-146967Fulltext
- https://liu.diva-portal.org/smash/get/diva2:1196098/FULLTEXT01.pdffulltext
- https://liu.diva-portal.org/smash/get/diva2:1196098/COVER01.pdfcover
- https://liu.diva-portal.org/smash/get/diva2:1196098/PREVIEW01.pngpreview image
- http://liu.diva-portal.org/smash/get/diva2:1196098/FULLTEXT01
- https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-146967
- https://doi.org/10.3384/diss.diva-146967
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