Closed and open state dependent block of potassium channels cause opposing effects on excitability – a computational approach
Autor: | Johanna Nilsson, Richard Ågren, Peter Århem |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Action Potentials lcsh:Medicine Ion channels in the nervous system Biophysical Phenomena Article Kv channel 03 medical and health sciences Mice Xenopus laevis 0302 clinical medicine Axon membrane Block (telecommunications) Potassium Channel Blockers Premovement neuronal activity Animals Humans lcsh:Science Neurons Biophysical methods Multidisciplinary Membranes Chemistry Sodium channel lcsh:R Computational Biology Models Theoretical Potassium channel Axons 030104 developmental biology State dependent Potassium Channels Voltage-Gated Cellular excitability Biophysics Potassium Calcium lcsh:Q Ion Channel Gating 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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