Decreased ATP-sensitive K+ current density during chronic human atrial fibrillation

被引:39
作者
Balana, B
Dobrev, D
Wettwer, E
Christ, T
Knaut, M
Ravens, U
机构
[1] Tech Univ Dresden, Dept Pharmacol & Toxicol, Carl Gustav Carus Med Sch, D-01307 Dresden, Germany
[2] Int Max Planck Res Sch Mol Cell Biol & Bioengn, D-01307 Dresden, Germany
[3] Tech Univ Dresden, Ctr Cardiovasc, D-01307 Dresden, Germany
关键词
atrial function; arrhythmia; human atrial myocytes; K-ATP channel;
D O I
10.1016/S0022-2828(03)00246-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Chronic atrial fibrillation (AF) is associated with shortening of action potential duration (APD), which involves modified activity of atrial ion currents. However. little is known about the activity of ATP-sensitive K+ channels (I-K,I-ATP) during chronic AE An AF-related increase in the activity of 1(K.ATP) would reduce APD and could contribute to initiation and/or perpetuation of AF. Here, we studied the activity of 1K,ATP in atrial myocytes from patients with sinus rhythm (SR) and chronic AF Human atrial myocytes were isolated from atrial tissue obtained from patients undergoing open-heart surgery. Inward rectifier currents were measured with the whole-cell patch-clamp technique by applying a depolarizing ramp pulse (1245 ms) from -100 to +40 mV (0.5 Hz). I-K,I-ATP was activated with the I-K,I-ATP channel opener rilmakalim. The inward rectifier I-K1 and I-K,I-ATP were identified by their sensitivity to 1 mM Ba2+. Density of I-K1 did not differ between cells from patients with AF (at -100 mV: -14.8 +/- 1.3 pA/pF, n = 38/10 (cells/patients)) and SR (-13.8 +/- 1.5 pA/pF, n = 33/16). In both types of cells, rilmakalim stimulated I-K,I-ATP (defined as rilmakalim-inducible current) in a concentration-dependent manner (0.3-10 muM). However, maximum activation of I-K,I-ATP with muM rilmakalim was smaller in AF than in SR cells (at -100 mV: -5.3 +/- 0.8 pA/pF, n = 22/7 vs. -11.2 +/- 2.9 pA/pF, n = 19/9; at +40 mV: +9.6 +/- 2.1 pA/pF. it = 22/7 vs. +23.7 +/- 3.4 pA/pF, n = 19/9 for AF and SR, respectively; P < 0.05). Only aortic valve disease and pulmonary hypertension were found to be independent contributors to I-K,I-ATP current density. We provide evidence that chronic AF is associated with a downregulation of ATP-sensitive K+ currents. These changes may provide an additional molecular mechanism for electrical remodeling in chronic AF (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1399 / 1405
页数:7
相关论文
共 34 条
  • [1] Toward understanding the assembly and structure of KATP channels
    Aguilar-Bryan, L
    Clement, JP
    Gonzalez, G
    Kunjilwar, K
    Babenko, A
    Bryan, J
    [J]. PHYSIOLOGICAL REVIEWS, 1998, 78 (01) : 227 - 245
  • [2] Changes in ultrastructural calcium distribution in goat atria during atrial fibrillation
    Ausma, J
    Dispersyn, GD
    Duimel, H
    Thoné, F
    Donck, LV
    Allessie, MA
    Borgers, M
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2000, 32 (03) : 355 - 364
  • [3] Ionic mechanisms of electrical remodeling in human atrial fibrillation
    Bosch, RF
    Zeng, XR
    Grammer, JB
    Popovic, K
    Mewis, C
    Kühlkamp, V
    [J]. CARDIOVASCULAR RESEARCH, 1999, 44 (01) : 121 - 131
  • [4] Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation:: Differential regulation of protein and mRNA levels for K+ channels
    Brundel, BJJM
    Van Gelder, IC
    Henning, RH
    Tuinenburg, AE
    Wietses, M
    Grandjean, JG
    Wilde, AAM
    Van Gilst, WH
    Crijns, HJGM
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2001, 37 (03) : 926 - 932
  • [5] Remodeling of cardiomyocyte ion channels in human atrial fibrillation
    Dobrev, D
    Ravens, U
    [J]. BASIC RESEARCH IN CARDIOLOGY, 2003, 98 (03) : 137 - 148
  • [6] Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation
    Dobrev, D
    Wettwer, E
    Kortner, A
    Knaut, M
    Schüler, S
    Ravens, U
    [J]. CARDIOVASCULAR RESEARCH, 2002, 54 (02) : 397 - 404
  • [7] Molecular basis of downregulation of G-protein-coupled inward rectifying K+ current (IK,ACh) in chronic human atrial fibrillation -: Decrease in GIRK4 mRNA correlates with reduced IK,ACh and muscarinic receptor-mediated shortening of action potentials
    Dobrev, D
    Graf, E
    Wettwer, E
    Himmel, HM
    Hála, O
    Doerfel, C
    Christ, T
    Schüler, S
    Ravens, U
    [J]. CIRCULATION, 2001, 104 (21) : 2551 - 2557
  • [8] G-protein β3-subunit 825T allele is associated with enhanced human atrial inward rectifier potassium currents
    Dobrev, D
    Wettwer, E
    Himmel, HM
    Kortner, A
    Kuhlisch, E
    Schüler, S
    Siffert, W
    Ravens, U
    [J]. CIRCULATION, 2000, 102 (06) : 692 - 697
  • [9] ALPHA-RECEPTOR CONSTRICTION INDUCED BY ATRIAL-FIBRILLATION DURING MAXIMAL CORONARY DILATATION
    ERTL, G
    WICHMANN, J
    KAUFMANN, M
    KOCHSIEK, K
    [J]. BASIC RESEARCH IN CARDIOLOGY, 1986, 81 (01) : 29 - 39
  • [10] PREVALENCE, AGE DISTRIBUTION, AND GENDER OF PATIENTS WITH ATRIAL-FIBRILLATION - ANALYSIS AND IMPLICATIONS
    FEINBERG, WM
    BLACKSHEAR, JL
    LAUPACIS, A
    KRONMAL, R
    HART, RG
    [J]. ARCHIVES OF INTERNAL MEDICINE, 1995, 155 (05) : 469 - 473