Ethanol increases the activity of large conductance, Ca(2+)-activated K+ channels in isolated neurohypophysial terminals.
Ethanol increases the activity of large conductance, Ca(2+)-activated K+ channels in isolated neurohypophysial terminals.
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DOI：
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发表时间：
1996
影响因子：
3.6
通讯作者：
A. Dopico;JoséR. Lemos;S. Treistman
中科院分区：
文献类型：
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作者：
A. Dopico;JoséR. Lemos;S. Treistman
大电导、Ca(2+) 激活的 K+ 通道被认为是爆发间隔的基础，因此有助于控制神经垂体末梢的激素释放。由于乙醇会抑制加压素和催产素的释放，因此我们使用膜片钳技术研究了其对这些末端的大电导、Ca(2+) 激活的 K+ 通道的影响。将乙醇 (10-100 mM) 应用于切除的由内而外的斑块的胞质表面，以浓度依赖性方式可逆地增加通道活性，在 50-100 mM 处达到稳定水平。这种激活不是由可自由扩散的胞质第二信使或细胞内储存的 Ca2+ 释放介导的。相反，它可能反映了乙醇与通道蛋白或密切相关的成分的直接相互作用。单一电导和电压-电流关系的特征都不会被药物改变。乙醇增加通道活性是由于通道门控特性的改变：长开放对开放状态总时间的贡献增加，快速开放的平均持续时间略有增加，并且长封闭在药物存在下消失。乙醇对大电导 Ca(2+) 激活的 K+ 通道的激活，与先前报道的电压依赖性 Ca2+ 通道的抑制相结合，可以解释乙醇摄入后加压素和催产素释放的减少。
Large conductance, Ca(2+)-activated K+ channels are believed to underlie interburst intervals and, thus, contribute to the control of hormone release from neurohypophysial terminals. Because ethanol inhibits the release of vasopressin and oxytocin, we studied its effects on large conductance, Ca(2+)-activated K+ channels from these terminals using patch-clamp techniques. Ethanol (10-100 mM) applied to the cytosolic surface of excised, inside-out patches reversibly increases channel activity in a concentration-dependent manner, reaching a plateau at 50-100 mM. This activation is not mediated by freely diffusible cytosolic second messengers or the release of Ca2+ from intracellular stores. Rather, it likely reflects a direct interaction of ethanol with the channel protein or a closely associated component. Neither the unitary conductance nor the characteristics of the voltage-current relationship are modified by the drug. The increase of channel activity by ethanol results from a modification of channel gating properties: the contribution of long openings to the total time spent in the open state is increased, the average duration of the fast openings is slightly increased, and long closures disappear in the presence of the drug. The activation of large conductance, Ca(2+)-activated K+ channels by ethanol, in conjunction with the previously reported inhibition of voltage-dependent Ca2+ channels, can explain the reduced release of vasopressin and oxytocin after ethanol ingestion.