TABLE 5

K2P5.1 channels

Channel name K2P5.1
Description Two-pore domain potassium channel subunit; open rectifier
Other names KCNK5, TASK-2
Molecular information Human: 499aa, NM_003740, chr. 6p21, KCNK5,1 GeneID: 8645, PMID: 98129781
Rat: not cloned
Mouse: 502aa, NM_021542, kcnk5
Associated subunits Not established
Functional assays Electrophysiological
Current Open rectifier
Conductance See “Comments”
Ion selectivity Not established
Activation See “Comments”
Inactivation See “Comments”
Activators Volatile anaesthetics2: halothane (∼570 mM)
Gating inhibitors None
Blockers Quinidine (22 mM), external pH (6.5),6 local anesthetics: lidocaine (1 mM), bupivacaine (1 mM), clofilium (25 μM)7
Radioligands None
Channel distribution Brain,3 kidney, liver, small intestine, pancreas, placenta
Physiological functions A role in cell volume regulation7,8 (see “Comments”) and sensing external basolateral pH changes associated with Formula transport in primary-cultured proximal tubular cells4
Mutations and pathophysiology Not established
Pharmacological significance Not established
Comments Activation and deactivation with voltage steps seem instantaneous; the conductance of K2P5 depends on the ionic conditions; the slope conductance was reported as 15pS with 5 mM external potassium and as high as 60pS when external potassium is high (155 mM)1 this may reflect an Na+-dependent inward rectification that becomes progressively less pronounced with time5; like K2P16 and 17, current through K2P5 channels is diminished at physiological pH; channel open probability increases with external pH; formation of an intersubunit disulfide bridge in K2P5 does not affect channel activity9; exposure to hypotonicity (change from 300—200 mOsm in external solution) enhanced mK2P5 currents when this channel was heterologously expressed in HEK293 cells, and osmotic cell shrinkage led to inhibition (change from 300—400 mOsm in external solution)

  • aa, amino acids; chr., chromosome.

  • ↵1. Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, and Lazdunski M (1998) Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J Biol Chem 273:30863-30869

  • ↵2. Gray AT, Zhao BB, Kindler CH, Winegar BD, Mazurek MJ, Xu J, Chavez RA, Forsayeth JR, and Yost CS (2000) Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5. Anesthesiology 92:1722-1730

  • ↵3. Gabriel A, Abdallah M, Yost CS, Winegar BD, and Kindler CH (2002) Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat central nervous system. Brain Res Mol Brain Res 98:153-163

  • ↵4. Warth R, Barriere H, Meneton P, Bloch M, Thomas J, Tauc M, Heitzmann D, Romeo E, Verrey F, Mengual R, et al. (2004) Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. Proc Natl Acad Sci USA 101:8215-8220

  • ↵5. Morton MJ, Chipperfield S, Abohamed A, Sivaprasadarao A, and Hunter M (2004) Na+-induced in ward rectification in the two-pore domain K+ channel, TASK-2. Am J Physiol Renal Physiol 288:F162-F169

  • ↵6. Kang DW and Kim D (2004) Single channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family. Biochem Biophys Res Comm 315:836-844

  • ↵7. Niemeyer MI, Cid LP, Barros LF, and Sepulveda FV (2001) Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. J Biol Chem 276:43166-43174

  • ↵8. Barriere H, Belfodil R, Rubera I, Tauc M, Lesage F, Poujeol C, Guy N, Barhanin J, and Poujeol P (2003) Role of TASK2 potassium channels regarding volume regulation in primary cultures of mouse proximal tubules. J Gen Physiol 122:177-190

  • ↵9. Niemeyer MI, Cid LP, Valenzuela X, Paeile V, and Sepulveda FV (2003) Extracellular conserved cysteine forms anointer subunit disulphide bridge in the KCNK5 (TASK-2) K+ channel without having an essential effect upon activity. Mol Membr Biol 20:185-191