ION-CHANNEL MODULATION BY NS-1619, THE PUTATIVE BK-CA CHANNEL OPENER, IN VASCULAR SMOOTH-MUSCLE
ION-CHANNEL MODULATION BY NS-1619, THE PUTATIVE BK-CA CHANNEL OPENER, IN VASCULAR SMOOTH-MUSCLE
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DOI：
10.1111/j.1476-5381.1994.tb17171.x
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发表时间：
1994-12-01
影响因子：
7.3
通讯作者：
WESTON, AH
中科院分区：
文献类型：
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作者：
EDWARDS, G;NIEDERSTEHOLLENBERG, A;WESTON, AH
1在大鼠完整门静脉和从同一组织酶促分离的单个平滑肌细胞上研究了NS 1619（假定的BKca通道开放剂）的作用。2在全细胞膜片钳条件下，使用富钾移液管，将单个细胞暴露于NS 1619，（10-33 μ M）诱导了一个嘈杂的，外向电流，达到最大值（33 μ M NS 1619;平均35.8 +/- 17 pA，n = 8），约6分钟内。3在步进测试电位时（范围-50至+50 mV）从-10 mV的保持电位，NS 1619诱导的噪声电流具有时间依赖性激活和明显的外向整流。4 NS 1619在- 10 mV刺激外向电流不依赖于Ca 2+的存在但是被槽液中的Charybdotoxin（250 nM）或penitrem A（100 nM）拮抗。5 NS 1619在- 10 mV诱导的噪声电流的稳态波动分析得出70 +/- 8 pS（n = 4）的值。（在实验的准生理条件下）对于所涉及的通道的单位电导。6At- 10 mV，NS 1619（10-33 μ M）迅速抑制自发瞬时外向电流。7在-90 mV的保持电位下，NS 1619（10-33 μ M）产生了由去极化步骤诱发的外向电流减少至+50 mV，这一效应与延迟整流电流的显著抑制有关，I-K（V）.8 NS 1619（3-100 μ M）对大鼠门静脉自发活动产生浓度依赖性抑制，其特征在于张力波的振幅和持续时间减少。这种抑制作用在Charybdotoxin（250 nM）或penitrem A（1 μ M）存在下略有增强。NS 1619对KCl引起的大鼠主动脉收缩也有明显的抑制作用（20 mM和80 mM）。9在全细胞记录条件下并使用富含Cs的移液管，门静脉细胞从-90 mV的保持电位步进到-30 ~+ mV的测试电位诱发的钙电流10 NS 1619（33 μ M）抑制左克罗卡林（10 μ M）对I-K（ATP）的诱导。11得出结论，NS 1619激活大电导、Ca 2+敏感性通道，BKca和在相同的浓度范围内，它抑制Kv和L-型钙通道。在大鼠门静脉和主动脉中观察到的NS 1619诱导的机械抑制似乎最可能是由于观察到的Ca电流抑制。
1 The effects of NS 1619, the putative BKca channel opener, were investigated on rat intact portal veins and on single smooth muscle cells enzymatically separated from the same tissue.2 Under whole-cell patch clamp conditions with K-rich pipettes, exposure of single cells held at -10 mV to NS 1619 (10-33 mu M) induced a noisy, outward current which reached a maximum (33 mu M NS 1619; mean 35.8 +/- 17 pA, n = 8) within about 6 min.3 On stepping to test potentials (range - 50 to + 50 mV) from a holding potential of - 10 mV, the NS 1619-induced noisy current exhibited time-dependent activation and marked outward rectification.4 The stimulation of outward currents by NS 1619 at - 10 mV was independent of the presence of Ca2+ in the bath or pipette solutions but was antagonized by either charybdotoxin (250 nM) or penitrem A (100 nM) in the bath solution.5 Stationary fluctuation analysis of the noisy current induced by NS 1619 at - 10 mV yielded a value of 70 +/- 8 pS (n = 4) (under the quasi-physiological conditions of the experiment) for the unitary conductance of the channel involved.6 At - 10 mV, NS 1619 (10-33 mu M) rapidly inhibited spontaneous transient outward currents.7 With a holding potential of - 90 mV, NS 1619 (10-33 mu M) produced a reduction of outward currents evoked by depolarizing steps to + 50 mV, an effect associated with marked inhibition of the delayed rectifier current, I-K(V).8 NS 1619 (3-100 mu M) produced a concentration-dependent inhibition of spontaneous activity in rat portal vein characterized by a reduction in the amplitude and duration of the tension waves. This inhibition was slightly potentiated in the presence of either charybdotoxin (250 nM) or penitrem A (1 mu M). NS 1619 also totally inhibited contractions of rat aorta induced by KCl (both 20 mM and 80 mM).9 Under whole-cell recording conditions and using Cs-rich pipettes, Ca-currents evoked in portal vein cells by stepping from a holding potential of - 90 mV to test potentials in the range - 30 to + 50 mV were totally inhibited in the presence of 33 mu M NS 1619.10 NS 1619 (33 mu M) inhibited the induction of I-K(ATP) by levcromakalim (10 mu M).11 It is concluded that NS 1619 activates the large conductance, Ca2+-sensitive channel, BKca and over the same concentration range it inhibits both Kv and L-type Ca-channels. The observed NS 1619-induced mechanical inhibition in rat portal vein and aorta seems most likely to be due to the observed inhibition of Ca-currents.