Three different potassium channels in human atrium. Contribution to the basal potassium conductance.

Three different potassium channels in human atrium. Contribution to the basal potassium conductance.
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人心房中三种不同的钾通道。

DOI:
10.1161/01.res.66.5.1277
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发表时间:
1990
影响因子:
20.1
通讯作者:
E. Carmeliet
E. Carmeliet
中科院分区:
医学1区
文献类型:
--
作者:
H. Heidbuchel;J. Vereecke;E. Carmeliet

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我们在对称等渗钾条件下对单个人(和豚鼠)心房细胞应用细胞贴附和内外膜片钳技术。人类细胞是通过先前描述的改良方法分离出来的。我们的目的有两个:1)研究在基础条件下(iK1和iK(ATP))或在10(-5)M乙酰胆碱刺激下存在的人心房单细胞钾通道的单通道特性;2)计算这三种通道类型对人心房细胞基底钾电导总量的贡献,并与相同条件下豚鼠心房细胞的数据进行比较。我们发现在人类细胞中,58%的斑块(n = 42/74)含有乙酰胆碱敏感的钾通道,它们的电导为42 +/- 1.2 pS,平均打开时间(tau o)为1.7 +/- 0.5 msec。在没有激动剂的情况下,它们表现出零星的开口,乙酰胆碱的激活依赖于g蛋白。在16%的斑块(n = 7/44)中,腺苷(10(-4)M)激活了相同的通道,但活性低于乙酰胆碱刺激。在18%的斑块(n = 9/51)中,存在iK1通道(电导,27 pS; tau, 8.7 msec),而在细胞附着模式中,从未见过atp依赖性通道。然而,在ATPi冲洗时,它们出现在一半的内向外斑块中(电导,73 pS; tau, 1.4 msec)。基础钾电导(即,在没有任何外源性激素或神经递质的情况下)主要是由于人类和豚鼠细胞中的iK1通道,这一发现与先前的报道相反。然而,乙酰胆碱诱导的钾电流在豚鼠体内比在人类分离细胞中高得多;它的一小部分就足以完全确定豚鼠心房细胞的静息钾电导,而它只能在人类细胞中发挥调节作用。这种差异在物种特异性自主神经调节和抗心律失常药物作用中可能是重要的。
We applied the cell-attached and inside-out patch-clamp technique under symmetrical isotonic potassium conditions on single human (and guinea pig) atrial cells. The human cells were isolated by a modified method to that described earlier. Our aim was twofold: 1) to study the single-channel characteristics of potassium channels in human atrial single cells, present under basal conditions (iK1 and iK(ATP] or when stimulated with 10(-5) M acetylcholine; and 2) to calculate the contribution of these three channel types to the total basal potassium conductance in human atrial cells, and to compare the results with data on guinea pig atrial cells under the same conditions. We found that in human cells 58% of the patches (n = 42/74) contained acetylcholine-sensitive potassium channels: their conductance was 42 +/- 1.2 pS and mean open time (tau o) was 1.7 +/- 0.5 msec. They showed sporadic openings in the absence of agonist, and activation by acetylcholine was G-protein dependent. In 16% of the patches (n = 7/44), adenosine (10(-4) M) activated the same channels, but the activity was lower than when stimulated by acetylcholine. In 18% of the patches (n = 9/51), an iK1 channel was present (conductance, 27 pS; tau o, 8.7 msec), whereas in the cell-attached mode, ATP-dependent channels were never seen. However, they were present in half of the inside-out patches on washout of ATPi (conductance, 73 pS; tau o, 1.4 msec). The basal potassium conductance (i.e., in the absence of any exogenous hormone or neurotransmitter) was mainly due to iK1 channels in both human and guinea pig cells, a finding that is in contrast with previous reports. However, the potassium current that is induced by acetylcholine is much higher in guinea pig than in human isolated cells; a fraction of it would suffice to fully determine the resting potassium conductance in guinea pig atrial cells, whereas it can play only a modulatory role in human cells. This difference could be important in species-specific autonomic modulation and antiarrhythmic drug action.
DOI: --
发表时间: 1987
期刊: Nature
影响因子: 64.8
作者:
D. Logothetis;Y. Kurachi;J. Galper;E. Neer;D. Clapham
通讯作者: D. Logothetis;Y. Kurachi;J. Galper;E. Neer;D. Clapham