Pharmacological activation and inhibition of Slack (Slo2.2) channels

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• 作者：Bo Yang ; Valentin K. Gribkoff ; Jennifer Pan ; Veronique Damagnez ; Steven I. Dworetzky ; Christopher G. Boissard ; Arin Bhattacharjee ; Yangyang Yan ; Fred J. Sigworth and Leonard K. Kaczmarek
• 关键词：Potassium channels ; Slack ; Sodium-activated channels ; Electrophysiology
• 刊名：Neuropharmacology
• 出版年：2006
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：September 2006
• 卷：51
• 期：4
• 页码：896-906
• 文件大小：648 K

摘要

The Slack (Sequence like a calcium-activated K channel) (Slo2.2) gene is abundantly expressed in the mammalian brain and encodes a sodium-activated K⁺ (K_Na) channel. Although the specific roles of Slack channel subunits in neurons remain to be identified, they may play a role in the adaptation of firing rate and in protection against ischemic injury. In the present study, we have generated a stable cell line expressing the Slack channel, and have analyzed the pharmacological properties of these channels in these cells and in Xenopus oocytes. Two known blockers of K_Na channels, bepridil and quinidine, inhibited Slack currents in a concentration-dependent manner and decreased channel activity in excised membrane patches. The inhibition by bepridil was potent, with an IC₅₀ of 1.0 μM for inhibition of Slack currents in HEK cells. In contrast, bithionol was found to be a robust activator of Slack currents. When applied to the extracellular face of excised patches, bithionol rapidly induced a reversible increase in channel opening, suggesting that it acts on Slack channels relatively directly. These data establish an important early characterization of agents that modulate Slack channels, a process essential for the experimental manipulation of Slack currents in neurons.