Characterization of an ultrarapid delayed rectifier potassium channel involved in canine atrial repolarization

被引:96
作者
Yue, LX
Feng, JL
Li, GR
Nattel, S
机构
[1] MONTREAL HEART INST,DEPT MED,MONTREAL,PQ H1T 1C8,CANADA
[2] UNIV MONTREAL,MONTREAL,PQ,CANADA
[3] MCGILL UNIV,DEPT PHARMACOL & THERAPEUT,MONTREAL,PQ,CANADA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1996年 / 496卷 / 03期
关键词
D O I
10.1113/jphysiol.1996.sp021716
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Depolarizing pulses positive to 0 mV elicit a transient outward current (I-to) and a sustained 'pedestal' current in canine atrial myocytes. The pedestal current was highly sensitive to 4-aminopyridine (4-AP) and TEA, with 50% inhibitory concentrations (EC(50)) of 5.3+/-0.74 and 307+/-05 mu m, respectively. When the pedestal current was separated from Ito with prepulses or by studying current sensitive to 10 mM TEA, it showed very rapid activation and deactivation. We therefore designated the current I-Kur,I-d, for 'ultrarapid delayed rectifier, dog'. I-Kur,I-d inactivation was bi-exponential, with mean time constants of 609+/-91 and 5563+/-676 ms during a 20 s pulse to +40 mV. 2. The reversal potential of I-Kur,I-d tail currents are dependent on extracellular potassium concentration ([K+](o); slope, 54.7 mV decade(-1)). The envelope of tails test was satisfied and the current inwardly rectified at greater than or equal to+40 mV. The current was insensitive to E-4031, dendrotoxin and chloride substitution, but was inhibited by barium, with an EC(50) of 1.65 mM. Lanthanum ions caused a positive shift in voltage dependence without producing direct inhibition. 3. Single-channel activity was observed in cell-attached, inside-out and outside-out patches. Upon depolarization form -50 to +30 mV, single channels had similar time constants and [K+](o) dependence to whole-cell current. Channel open probability (P-o) increased with depolarization in a saturable fashion and the P-o-voltage relation had a half-activation voltage and slope factor similar to whole-cell I-Kur,I-d. 4. Unitary channel current was linearly related to depolarization potential to +40 mV; at more positive potentials, inward rectification occurred. The unitary conductance was 20.3 and 35.5 pS for an [K+](o) of 5.4 and 130 mM, respectively. Single-channel activity was strongly inhibited by 50 mu M 4-AP or 10 mM TEA. Both 4-AP and TEA decreased open time, suggesting open-channel block. 5. Selective inhibition of I-Kur,I-d with 50 mu m 4-AP or 0.3-5 mM TEA prolonged canine atrial action potentials, indicating that I-Kur,I-d contributes to canine atrial repolarization. The single-channel and macroscopic properties of I-Kur,I-d have many similarities to those of currents carried by Kv3.1 cloned channels and our findings thus suggest a possible role for Kv3.1 channels in cardiac repolarization.
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收藏
页码:647 / 662
页数:16
相关论文
共 27 条
[1]   CHARACTERIZATION OF 2 DISTINCT DEPOLARIZATION-ACTIVATED K+ CURRENTS IN ISOLATED ADULT-RAT VENTRICULAR MYOCYTES [J].
APKON, M ;
NERBONNE, JM .
JOURNAL OF GENERAL PHYSIOLOGY, 1991, 97 (05) :973-1011
[2]   BACKGROUND POTASSIUM CURRENT ACTIVE DURING THE PLATEAU OF THE ACTION-POTENTIAL IN GUINEA-PIG VENTRICULAR MYOCYTES [J].
BACKX, PH ;
MARBAN, E .
CIRCULATION RESEARCH, 1993, 72 (04) :890-900
[3]   TIME-DEPENDENT OUTWARD CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES - GATING KINETICS OF THE DELAYED RECTIFIER [J].
BALSER, JR ;
BENNETT, PB ;
RODEN, DM .
JOURNAL OF GENERAL PHYSIOLOGY, 1990, 96 (04) :835-863
[4]   A NOVEL TYPE OF DEPOLARIZATION-ACTIVATED K+ CURRENT IN ISOLATED ADULT-RAT ATRIAL MYOCYTES [J].
BOYLE, WA ;
NERBONNE, JM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 260 (04) :H1236-H1247
[5]  
CAMPBELL DL, 1995, CARDIAC ELECTROPHYSI, P83
[6]   2 TYPES OF POTASSIUM CHANNELS IN MURINE LYMPHOCYTES-T [J].
DECOURSEY, TE ;
CHANDY, KG ;
GUPTA, S ;
CAHALAN, MD .
JOURNAL OF GENERAL PHYSIOLOGY, 1987, 89 (03) :379-404
[7]   IDENTITY OF A NOVEL DELAYED RECTIFIER CURRENT FROM HUMAN HEART WITH A CLONED K+ CHANNEL CURRENT [J].
FEDIDA, D ;
WIBLE, B ;
WANG, Z ;
FERMINI, B ;
FAUST, F ;
NATTEL, S ;
BROWN, AM .
CIRCULATION RESEARCH, 1993, 73 (01) :210-216
[8]  
GRISSMER S, 1992, J BIOL CHEM, V267, P20971
[9]  
GRISSMER S, 1994, MOL PHARMACOL, V45, P1227
[10]   3 DIFFERENT POTASSIUM CHANNELS IN HUMAN ATRIUM - CONTRIBUTION TO THE BASAL POTASSIUM CONDUCTANCE [J].
HEIDBUCHEL, H ;
VEREECKE, J ;
CARMELIET, E .
CIRCULATION RESEARCH, 1990, 66 (05) :1277-1286