Quantitative modeling of 4-aminopyridine block of transient outward current
Result description
The 4-aminopyridine (4-AP) sensitive component of transient outward current (Ito) is a prominent modulator of repolarization phase of cardiac action potential. The inhibition of cardiac Ito is characterised by reverse use dependency which has been tentatively explained as a result of high affinity of the drug to the open and the resting channel and unattainability of block in the inactivated state [1]. With the aim to explain the experimental data, we have proposed a quantitative model (see the kineticscheme) based on the following presumptions: 1. Only charged (protonated) 4-AP molecules have access to their receptor through the open channel and bind in a voltage dependent manner (O-B0+). 2. The protonation and deprotonation of the drug molecule canoccur even in the blocked open channel (B0+-B0). 3. The effect of block on the operation of activating gates is negligible. 4. The drug-receptor interaction in the closed channels is voltage ndependent (B1-C1)
Keywords
Quantitative modeling4-aminopyridineblocking effecttransient outward current
The result's identifiers
Result code in IS VaVaI
Result on the web
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DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
Quantitative modeling of 4-aminopyridine block of transient outward current
Original language description
The 4-aminopyridine (4-AP) sensitive component of transient outward current (Ito) is a prominent modulator of repolarization phase of cardiac action potential. The inhibition of cardiac Ito is characterised by reverse use dependency which has been tentatively explained as a result of high affinity of the drug to the open and the resting channel and unattainability of block in the inactivated state [1]. With the aim to explain the experimental data, we have proposed a quantitative model (see the kineticscheme) based on the following presumptions: 1. Only charged (protonated) 4-AP molecules have access to their receptor through the open channel and bind in a voltage dependent manner (O-B0+). 2. The protonation and deprotonation of the drug molecule canoccur even in the blocked open channel (B0+-B0). 3. The effect of block on the operation of activating gates is negligible. 4. The drug-receptor interaction in the closed channels is voltage ndependent (B1-C1)
Czech name
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Czech description
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Classification
Type
Jx - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
BO - Biophysics
OECD FORD branch
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Result continuities
Project
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
1999
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Physiological Research
ISSN
0862-8408
e-ISSN
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Volume of the periodical
48
Issue of the periodical within the volume
Suppl 1
Country of publishing house
CZ - CZECH REPUBLIC
Number of pages
1
Pages from-to
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UT code for WoS article
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EID of the result in the Scopus database
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Basic information
Result type
Jx - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP
BO - Biophysics
Year of implementation
1999