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Blockade of the delayed rectifier K+ currents, IKr, in rabbit sinoatrial node cells by external divalent cations

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Author(s)
Dae-Kyu SongYung E. EarmWon-Kyung Ho
Keimyung Author(s)
Song, Dae Kyu
Department
Dept. of Physiology (생리학)
Institute for Medical Science (의과학연구소)
Journal Title
Pflügers Archiv - European Journal of Physiology
Issued Date
1999
Volume
438
Issue
2
Keyword
Channel blockadeDelayed rectifier K+currentsDivalent cationsHeartSinoatrial node
Abstract
We investigated the actions of various divalent
cations on the delayed rectifier K+ currents (IKr) in rabbit
sinoatrial node cells using the whole-cell voltage-clamp
technique in isotonic K+ solutions. External divalent cations
decreased the amplitude of currents, accelerated the
time course of deactivation and shifted the activation to
positive potentials in a dose-dependent manner. The concentrations
for half-maximum inhibition of the steadystate
currents (KM) obtained at 0 mV were 0.63, 1.36,
1.65 and 2.16 mM for Ni2+, Co2+, Mn2+ and Ba2+, respectively.
The effect was voltage dependent (KM decreased
e-fold for 12.2–16.8 mV hyperpolarization), but
the dependence did not vary significantly among different
cations. Acceleration of the time course of current
deactivation by the increase of divalent cation concentration
was well fitted by the voltage-dependent block model,
and the binding rate constant (k1) was obtained. The
binding rates for the ions took the following order: Ni2+
>Co2+ >Mn2+ >Ba2+. The degree of the shift of activation
occurred in the same order: Ni2+ >Co2+ >Mn2+ >Ba2+.
From these results, we conclude that IKr channels are
non-selectively blocked by most divalent cations from
the external side and that the binding site is located deep
inside the channel, resulting in a steep voltage dependence
of the blockade.
Key words Channel blockade · Delayed rectifier K+
currents · Divalent cations · Heart · Sinoatrial node
Keimyung Author(s)(Kor)
송대규
Publisher
School of Medicine
Citation
Dae-Kyu Song et al. (1999). Blockade of the delayed rectifier K+ currents, IKr, in rabbit sinoatrial node cells by external divalent cations. Pflügers Archiv - European Journal of Physiology, 438(2), 147–153. doi: 10.1007/s004240050892
Type
Article
ISSN
0031-6768
Source
https://link.springer.com/article/10.1007%2Fs004240050892
DOI
10.1007/s004240050892
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33662
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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