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Closed and open state dependent block of potassium channels cause opposing effects on excitability - a computational approach
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
2019 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, nr 1, artikel-id 8175Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Block of voltage-gated potassium (Kv) channels has been demonstrated to affect neuronal activity described as increasing excitability. The effect has been associated with a closed-state dependent block. However, the block of Kv channels in e.g. local anesthetic and antiarrhythmics, is open state-dependent. Since the reduced excitability in this case mainly is due to sodium channel block, the role of the Kv channel block is concealed. The present investigation aims to analyse the specific role of state-dependent Kv channel block for excitability. Using a computational approach, with introduced blocked states in the Kv channel of the Frankenhaeuser-Huxley axon membrane model, we calculated the effects on threshold, firing and presynaptic Ca influx. The Ca influx was obtained from an N-type Cav channel model linked to the Frankenhaeuser-Huxley membrane. The results suggested that a selective block of open Kv channels decreased the rate of repetitive firing and the consequent Ca influx, thus challenging the traditional view. In contrast, presence of a closed-state block, increased the firing rate and the Ca influx. These findings propose that Kv channel block may either increase or decrease cellular excitability, thus highlighting the importance of further investigating the role of state-specific blocking mechanisms.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2019. Vol. 9, nr 1, artikel-id 8175
Nationell ämneskategori
Biofysik
Identifikatorer
URN: urn:nbn:se:oru:diva-74618DOI: 10.1038/s41598-019-44564-xISI: 000469912700016PubMedID: 31160624Scopus ID: 2-s2.0-85066621591OAI: oai:DiVA.org:oru-74618DiVA, id: diva2:1320779
Forskningsfinansiär
Vetenskapsrådet, 15083 21785-01-4Karolinska Institutets ForskningsstiftelseStockholms läns landsting
Anmärkning

Funding Agencies:

Division of Picture and Function

Karolinska University Hospital, Stockholm, Sweden

Tillgänglig från: 2019-06-05 Skapad: 2019-06-05 Senast uppdaterad: 2019-06-20Bibliografiskt granskad

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