Characterization of a hyperpolarization-activated time-dependent potassium current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium

被引:133
作者
Ehrlich, JR
Cha, TJ
Zhang, LM
Chartier, D
Villeneuve, L
Hébert, TE
Nattel, S
机构
[1] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada
[2] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
[3] Univ Montreal, Dept Anesthesiol, Montreal, PQ H3C 3J7, Canada
[4] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3A 2T5, Canada
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2004年 / 557卷 / 02期
关键词
D O I
10.1113/jphysiol.2004.061119
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cardiomyocytes from the pulmonary vein sleeves (PVs) are known to play an important role in atrial fibrillation. PVs have been shown to exhibit time-dependent hyperpolarization-induced inward currents of uncertain nature. We observed a time-dependent K+ current upon hyperpolarization of PV and left atrial (LA) cardionryocytes (I-KH) and characterized its biophysical and pharmacological properties. The activation time constant was weakly voltage dependent, ranging from 386 +/- 14 to 427 +/- 37 ms between - 120 and -90 mV, and the half-activation voltage averaged - 93 +/- 4 mV. I-KH was larger in PV than LA cells (e.g. at - 120 mV: - 2.8 +/- 0.3 versus - 1.9 +/- 0.2 pA pF(-1), respectively, P < 0.01). The reversal potential was similar to - 84 mV with 5.4 mm [K+] (o) and changed by 55.7 +/- 2.4 mV per decade [K+](o) change. I-KH was exquisitely Ba2+ sensitive, with a 50% inhibitory concentration (IC50) of 2.0 +/- 0.3 mum (versus 76.0 +/- 17.9 mum for instantaneous inward-rectifier current, P < 0.01), and showed similar Cs+ sensitivity to instantaneous current. I-KH was potently blocked by tertiapin-Q, a selective Kir3-subunit channelblocker(IC50 10.0 +/- 2.1 nm), was unaffected by atropine and was significantly-increased by isoproterenol (isoprenaline), carbachol and the non-hydrolysable guanosine triphosphate analogue GTPgammaS. I-KH activation by carbachol required GTP in the pipette and was prevented by pertussis toxin pretreatment. Tertiapin-Q delayed repolarization in atropine-exposed multicellular atrial preparations studied with standard microelectrodes (action potential duration pre- versus post-tertiapin-Q: 190.4 +/- 4.3 versus 234.2 +/- 9.9 ms, PV;202.6 +/- 2.6 versus 242.7 +/- 6.2 ms, LA; 2 Hz, P < 0.05 each). Seven-day atrial tachypacing significantly increased I-KH (e.g. at - 120 mV in PV: from -2.8 +/- 0.3 to -4.5 +/- 0.5 pA pF(-1), P < 0.01). We conclude that I-KH is a time-dependent, hyperpolarization-activated K+ current that likely involves Kir3 subunits and appears to play a significant role in atrial physiology.
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页码:583 / 597
页数:15
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