Besides TRPV1 and ASICs, two-pore (or tandem-pore) domain potassium (KCNK) channels may function as chemo- and mechanosensors of afferent neurons. Thus, many members of this family belonging to the tandem of pore domains in a weak inwardly rectifying K+ channel (TWIK), TWIK-related K+ channel (TREK), TWIK-related acid sensitive K+ channel (TASK), and TWIK-related arachidonic acid-stimulated K+ channel (TRAAK) subfamilies are found in DRG neurons and in the GI tract of humans and rats (97). Their basic function is to operate as background channels that play a role in setting the resting membrane potential and the excitability of neurons (170,171). In addition, several KCNK channels are extremely sensitive to variations in the extracellular or intracellular pH in a narrow physiologic range (97). Some of them, such as TREK, are also mechan-osensitive (172,173).
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