Oxygen and mitochondrial inhibitors modulate both monomeric and heteromeric TASK‐1 and TASK‐3 channels in mouse carotid body type‐1 cells. (23rd October 2013)

• Record Type: Journal Article
• Authors: Turner, Philip J.; Buckler, Keith J.
• Is Part Of: Journal of physiology. Volume 591:Number 23(2013:Dec.)
• Page Start: 5977
• Page End: 5998
• Publication Date: 2013-10-23
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2013.262022
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Key points</title> <p> <list id="l1" list-type="simple"> <list-item> <label> </label> <p>TASK‐like background potassium channels play a key role in the sensing of hypoxic, metabolic and acidic stimuli in arterial chemoreceptor cells.</p> </list-item> <list-item> <label> </label> <p>In this study, we investigated the roles of TASK‐1 and TASK‐3 in forming these channels by using gene deletion in mice.</p> </list-item> <list-item> <label> </label> <p>Deletion of <italic>Task‐1</italic> (<italic>Kcnk3</italic>) and/or <italic>Task‐3</italic> (<italic>Kcnk9</italic>) disrupted the main form of background K‐channel activity.</p> </list-item> <list-item> <label> </label> <p>In single knock‐out mice, we observed, instead of the wild‐type channel, the homomeric forms of TASK‐1 in <italic>Task‐3<sup>−/−</sup></italic> and TASK‐3 in <italic>Task‐1<sup>−/−</sup>.</italic></p> </list-item> <list-item> <label> </label> <p>All forms of TASK were inhibited by hypoxia, cyanide and the uncoupler FCCP.</p> </list-item> <list-item> <label> </label> <p>We conclude that the main form of background K‐channel in chemoreceptor cells is a TASK‐1/TASK‐3 heterodimer and that both TASK‐1 and TASK‐3 subunits can couple to both oxygen and metabolic signalling pathways in these cells.</p> </list-item> </list> </p> <p> <bold>Abstract </bold> In rat arterial chemoreceptors, background potassium channels play an important role in maintaining resting membrane potential and promoting depolarization and excitation in response to hypoxia or acidosis. It has been suggested that these channels are a heterodimer of TASK‐1 and TASK‐3 based on their similarity to heterologously expressed TASK‐1/3 fusion proteins. In this study, we sought to confirm the identity of these channels through germline ablation of <italic>Task‐1</italic> (<italic>Kcnk3</italic>) and <italic>Task‐3</italic> (<italic>Kcnk9</italic>) in mice. Background K‐channels were abundant in carotid body type‐1 cells from wild‐type mice and comparable to those previously described in rat type‐1 cells with a main conductance state of 33 pS. This channel was absent from both <italic>Task‐1<sup>−/−</sup></italic> and <italic>Task‐3<sup>−/−</sup></italic> cells. In its place we observed a larger (38 pS) K<sup>+</sup>‐channel in <italic>Task‐1<sup>−/−</sup></italic> cells and a smaller (18 pS) K<sup>+</sup>‐channel in <italic>Task‐3<sup>−/−</sup></italic> cells. None of these channels were observed in <italic>Task‐1<sup>−/−</sup></italic>/<italic>Task‐3<sup>−/−</sup></italic> double knock‐out mice. We therefore conclude that the predominant background K‐channel in wild‐type mice is a TASK‐1/TASK‐3 heterodimer, whereas that in <italic>Task‐1<sup>−/−</sup></italic> mice is TASK‐3 and, conversely, that in <italic>Task‐3<sup>−/−</sup></italic> mice is TASK‐1. All three forms of TASK channel in type‐1 cells were inhibited by hypoxia, cyanide and the uncoupler FCCP, but the greatest sensitivity was seen in TASK‐1 and TASK‐1/TASK‐3 channels. In summary, the background K‐channel in type‐1 cells is predominantly a TASK‐1/TASK‐3 heterodimer. Although both TASK‐1 and TASK‐3 are able to couple to the oxygen and metabolism sensing pathways present in type‐1 cells, channels containing TASK‐1 appear to be more sensitive.</p> </abstract>