Quantitative modeling of 4-aminopyridine block of transient outward current

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26220%2F99%3A4360033" target="_blank" >RIV/00216305:26220/99:4360033 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Quantitative modeling of 4-aminopyridine block of transient outward current

Popis výsledku v původním jazyce

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)

Název v anglickém jazyce

Quantitative modeling of 4-aminopyridine block of transient outward current

Popis výsledku anglicky

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)

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

BO - Biofyzika

OECD FORD obor

—

Projekt

<a href="/cs/project/GA305%2F97%2F0043" target="_blank" >GA305/97/0043: Iontové membránové proudy srdečních buněk v procesu elektrické a mechanické restituce</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

1999

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological Research

ISSN

0862-8408

e-ISSN

—

Svazek periodika

48

Číslo periodika v rámci svazku

Suppl 1

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

1

Strana od-do

—

Kód UT WoS článku

—

EID výsledku v databázi Scopus

—