Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra

Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra
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甲芬那酸对猪近端尿道平滑肌细胞钾电流的多重影响

DOI:
10.1038/sj.bjp.0705524
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发表时间:
2003
影响因子:
7.3
通讯作者:
Y. Ito
Y. Ito
中科院分区:
医学2区
文献类型:
--
作者:
N. Teramoto;Alison F. Brading;Y. Ito

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使用膜片钳技术(传统的全细胞、细胞贴壁、从外到外和从内到外配置)研究了甲芬那酸对猪尿道肌细胞膜电位和 K+ 电流的影响。在电流钳模式下,甲芬那酸引起浓度依赖性超极化,预用 1 μM 格列本脲可抑制这种超极化。在电压钳模式下,甲芬那酸诱导了一种外向电流,即使在-50 mV的伊比利亚毒素(IbTX,300 nM)存在下,该电流也被格列本脲阻断。 ATP 敏感的 K+ 通道(KATP 通道)可以在同一贴片中被甲芬那酸和 levcromakalim 激活,在细胞贴壁配置中具有相同的单一振幅和相似的开放门控(-50 mV)。在outside-out记录中,外用甲芬那酸激活细胞内Ca2+激活的IbTX敏感大电导K+通道(BKCa通道)。甲芬那酸 (30 μM) 激活自发瞬态外向电流 (STOC)。相比之下,甲芬那酸 (100 μM) 会增加持续的外向电流,从而降低 STOC 的活性。在整个电压范围内,在存在和不存在 5 μM 格列本脲的情况下,甲芬那酸对膜电流产生相反的影响。在 10 mM 4-氨基吡啶 (4-AP) 存在下,甲芬那酸仅增加外向电流。这些结果表明,甲芬那酸增加了猪尿道肌细胞中两种不同类型 K+ 通道(即 BKCa 通道和 KATP 通道)的通道活性,并减少了 4-AP 敏感 K+ 通道。
The effects of mefenamic acid on both membrane potential and K+ currents in pig urethral myocytes were investigated using patch‐clamp techniques (conventional whole‐cell, cell‐attached, outside‐out and inside‐out configuration). In the current‐clamp mode, mefenamic acid caused a concentration‐dependent hyperpolarization, which was inhibited by preapplication of 1 μM glibenclamide. In the voltage‐clamp mode, mefenamic acid induced an outward current that was blocked by glibenclamide even in the presence of iberiotoxin (IbTX, 300 nM) at −50 mV. ATP‐sensitive K+ channels (KATP channels) could be activated in the same patch by mefenamic acid and levcromakalim, with the same unitary amplitude and the similar opening gating at −50 mV in cell‐attached configuration. In outside‐out recording, external application of mefenamic acid activated intracellular Ca2+‐activated IbTX‐sensitive large‐conductance K+ channels (BKCa channels). Mefenamic acid (30 μM) activated spontaneous transient outward currents (STOCs). In contrast, mefenamic acid (100 μM) increased sustained outward currents, diminishing the activity of STOCs. Over the whole voltage range, mefenamic acid caused opposite effects on the membrane currents in the absence and presence of 5 μM glibenclamide. In the presence of 10 mM 4‐aminopyridine (4‐AP), mefenamic acid only increased the outward currents. These results indicate that mefenamic acid increases the channel activities of two distinct types of K+ channels (i.e. BKCa channels and KATP channels) and decreased 4‐AP‐sensitive K+ channels in pig urethral myocytes.
吡那地尔、克罗卡林和格列本脲对兔主动脉 Ca(2) 激活的 K 通道的调节。
DOI: 10.1152/ajpcell.1993.264.5.c1119
发表时间: 1993
期刊: The American journal of physiology
影响因子: --
作者:
Gelband,GH;McCullough,JR
通讯作者: McCullough,JR
来自兔主动脉的 Ca2 激活 K 通道:cromakalim 的调节。
DOI: 10.1016/0014-2999(89)90580-3
发表时间: 1989
影响因子: 5
作者:
Gelband,CH;Lodge,NJ;VanBreemen,C
通讯作者: VanBreemen,C
DOI: 10.1016/s0006-3495(87)83298-8
发表时间: 1987-12-01
影响因子: 3.4
作者:
SIGWORTH, FJ;SINE, SM
通讯作者: SINE, SM
DOI: 10.1016/s0006-3495(94)80712-x
发表时间: 1994-12-01
影响因子: 3.4
作者:
OTTOLIA, M;TORO, L
通讯作者: TORO, L