TRAAK is an ion channel from the two-pore domain potassium (K_2P) channel family with roles in maintaining the resting membrane potential and fast action potential conduction. Regulated by a wide range of physical and chemical stimuli, the affinity and selectivity of K_2P4.1 toward lipids remains poorly understood. Here we show the two isoforms of K_2P4.1 have distinct binding preferences for lipids dependent on acyl chain length and position on the glycerol backbone. The channel can also discriminate the fatty acid linkage at the SN₁ position. Of the 33 lipids interrogated using native mass spectrometry, phosphatidic acid had the lowest equilibrium dissociation constants for both isoforms of K_2P4.1. Liposome potassium flux assays with K_2P4.1 reconstituted in defined lipid environments show that those containing phosphatidic acid activate the channel in a dose-dependent fashion. Our results begin to define the molecular requirements for the specific binding of lipids to K_2P4.1.

TRAAK 是来自双孔结构域钾 (K _2P ) 通道家族的离子通道，具有维持静息膜电位和快速动作电位传导的作用。在广泛的物理和化学刺激的调节下，K _2P 4.1 对脂质的亲和力和选择性仍然知之甚少。在这里，我们展示了 K _2P 4.1 的两种同种型对依赖于酰基链长度和甘油主链位置的脂质的不同结合偏好。_{该通道还可以区分 SN 1}位置的脂肪酸键。在使用天然质谱法检测的 33 种脂质中，磷脂酸对于 K _{2P的两种同工型具有最低的平衡解离常数}4.1。_{在确定的脂质环境中重组 K 2P} 4.1 的脂质体钾通量测定表明，含有磷脂酸的那些以剂量依赖性方式激活通道。我们的结果开始确定脂质与 K _2P 4.1 特异性结合的分子要求。