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Untersuchung der σ-Pore in spannungsabhängigen hKv-Kanälen

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Erstveröffentlichung
2018-09-03
DOI
10.18725/OPARU-9525
Dissertation


Authors
Tyutyaev, Pavel
Referee
Grissmer, Stephan
Föhr, Karl
Faculties
Medizinische Fakultät
Institutions
Institut für Angewandte Physiologie
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https://oparu.uni-ulm.de/xmlui/license_v3
Abstract
Current through the σ-pore was first detected in hKv1.3_V388C channels, where the V388C mutation in hKv1.3 channels opened a new pathway (σ-pore) behind the central α-pore. Typical for this mutant channel was inward current at potentials more negative than -100 mV when the central α-pore was closed. The α-pore blockers such as TEA+ and peptide toxins (CTX, MTX) could not reduce current through the σ-pore of hKv1.3_V388C channels. This new pathway would proceed in parallel to the α-pore in the S6-S6 interface gap. To see whether this phenomenon is restricted to hKv1.3 channels we mutated hKv1.2 at the homologue position (hKv1.2_V370C). By overexpression of hKv1.2_V370C mutant channels in COS-7 cells we could show typical σ-currents. The electrophysiological properties of the σ-pore in hKv1.3_V388C and hKv1.2_V370C mutant channels were similar. The σ-pore of hKv1.2_V370C channels was most permeable to Na+ and Li+ whereas Cl- and protons did not influence current through the σ-pore. Tetraethylammonium (TEA+), charybdotoxin (CTX) and maurotoxin (MTX), known α-pore blockers, could not reduce current through the σ-pore of hKv1.2_V370C channels. Taken together we conclude that the observation of σ-pore currents is not restricted to Kv1.3 potassium channels but can also be observed in a closely related potassium channel. This finding could have implications in the treatment of different ion channel diseases linked to mutations of the respective channels in regions close to homologue position investigated by us.
Date created
2017
Subject Headings
Ionenkanal [GND]
Ion channels [MeSH]
Dewey Decimal Group
DDC 610 / Medicine & health

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Tyutyaev, Pavel (2018): Untersuchung der σ-Pore in spannungsabhängigen hKv-Kanälen. Open Access Repositorium der Universität Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-9525

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