“…Only a few relatively specific modulators of K 2P channel activity have been described so far. Sanshool (Bautista et al , ), isobutylalkenyl amide (Tulleuda et al , ), lamotrigine (Kang et al , ; Liu et al , ), aristolochic acid (Veale and Mathie, ), zinc and mercuric ions (Czirják and Enyedi, ), capsaicin (Beltran et al , ), loratadine (Bruner et al , ), flufenamic acid (Monteillier et al , ) and other antidepressant or nonsteroidal anti‐inflammatory drugs (Park et al , ) have been well documented to modulate TRESK activity; however, they are also known to influence other pharmacological targets in addition to this K 2P channel. A possible explanation for the lack of specific and high‐affinity pharmacological tools could be the extracellular cap domain found in the structure of K 2P channels which prevents free access to the extracellular side of the pore domain (Brohawn et al , ; Miller and Long, ).…”