Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated from the rat cerebellum cDNA library a complementary DNA encoding a new member of the tandem pore K(+) channel family. Its amino acid sequence shares 54% identity with that of TASK-1, but less than 30% with those of TASK-2 and other tandem pore K(+) channels (TWIK, TREK, TRAAK). Therefore, the new clone was named TASK-3. Reverse transcriptase-polymerase chain reaction analysis showed that TASK-3 mRNA is expressed in many rat tissues including brain, kidney, liver, lung, colon, stomach, spleen, testis, and skeletal muscle, and at very low levels in the heart and small intestine. When expressed in COS-7 cells, TASK-3 exhibited a time-independent, noninactivating K(+)-selective current. Single-channel conductance was 27 pS at -60 mV and 17 pS at 60 mV in symmetrical 140 mM KCl. TASK-3 current was highly sensitive to changes in extracellular pH (pH(o)), a hallmark of the TASK family of K(+) channels. Thus, a change in pH(o) from 7.2 to 6.4 and 6.0 decreased TASK-3 current by 74 and 96%, respectively. Mutation of histidine at position 98 to aspartate abolished pH(o) sensitivity. TASK-3 was blocked by barium (57%, 3 mM), quinidine (37%, 100 microM), and lidocaine (62%, 1 mM). Thus, TASK-3 is a new member of the acid-sensing K(+) channel subfamily (TASK).
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PMID:TASK-3, a new member of the tandem pore K(+) channel family. 1073 76

Tandem pore domain acid-sensitive K(+) channel 3 (TASK-3) is a new member of the tandem pore domain potassium channel family. A cDNA encoding a 365- amino acid polypeptide with four putative transmembrane segments and two pore regions was isolated from guinea pig brain. An orthologous sequence was cloned from a human genomic library. Although TASK-3 is 62% identical to TASK-1, the cytosolic C-terminal sequence is only weakly conserved. Analysis of the gene structure identified an intron within the conserved GYG motif of the first pore region. Reverse transcriptase-polymerase chain reaction analysis showed strong expression in brain but very weak mRNA levels in other tissues. Cell-attached patch-clamp recordings of TASK-3 expressed in HEK293 cells showed that the single channel current-voltage relation was inwardly rectifying, and open probability increased markedly with depolarization. Removal of external divalent cations increased the mean single channel current measured at -100 mV from -2.3 to -5.8 pA. Expression of TASK-3 in Xenopus oocytes revealed an outwardly rectifying K(+) current that was strongly decreased in the presence of lower extracellular pH. Substitution of the histidine residue His-98 by asparagine or tyrosine abolished pH sensitivity. This histidine, which is located at the outer part of the pore adjacent to the selectivity filter, may be an essential component of the extracellular pH sensor.
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PMID:TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor. 1074 66

Background K+ channels whose subunit contains four transmembrane segments and two pore-forming domains (4TM/2P) have been cloned recently. We studied whether 4TM/2P K+ channels are functionally expressed in astrocytes that are known to have a large background (resting) K+ conductance and a large resting membrane potential. Reverse transcriptase-PCR analysis showed that, among five 4TM/2P K+ channels examined, TASK-1, TASK-3 and TREK-2 mRNAs were expressed in cultured astrocytes from rat cortex. In cell-attached patches, we mainly observed three K+ channels with single-channel conductances of 30, 117 and 176 pS (-40 mV) in symmetrical 140 mM KCl. The 30 pS channel was the inward rectifying K+ channel that has been previously described in astrocytes. The 117 pS K+ channel also showed inward rectification and was insensitive to 1 mM tetraethylammonium and 1 mM 4-aminopyridine. The 176 pS channel was the Ca2+-activated K+ channel. The 117 pS K+ channel was determined to be TREK-2, as judged by its electrophysiological properties and activation by membrane stretch, free fatty acids and intracellular acidosis. In approximately 50% of astrocytes in culture, whole-cell K+ current increased markedly following application of arachidonic acid. The number of TREK-2 channels in these cells was estimated to be approximately 500-1000/cell. Our results show that TREK-2 is functionally expressed in cortical astrocytes in culture, and suggest that TREK-2 may be involved in K+ homeostasis of astrocytes during pathological states.
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PMID:Functional expression of TREK-2 K+ channel in cultured rat brain astrocytes. 1189 89

Insulin secretion from pancreatic beta cells is partly regulated by cell membrane potential. Background K+ channels that stabilize the resting membrane potential would suppress excitability and insulin secretion. Recent studies show that members of the two-pore domain K+ (K2P) channel family behave as background K+ channels in many excitable cells. Therefore, the expression of K2P channels was studied in insulin-secreting MIN6 cells. Reverse transcriptase PCR showed that, among nine K2P channels tested, TASK-1, TASK-2, TASK-3, TREK-2, and TRESK-2 were expressed in MIN6 cells. Cell-attached recordings on MIN6 cells revealed five types of K+ channels that were open at rest. Two were ATP-sensitive and Ca2+-activated K+ channels, as judged by their sensitivity to ATP and Ca2+, respectively, and single-channel conductance. Among five K2P channels, only TREK-2 could be clearly identified in MIN6 cells. The molecular identity of two other K+ channels is not yet known. TREK-2 in MIN6 cells was activated by arachidonic acid, membrane stretch, and low pH solution (pH 5.8). Arachidonic acid increased Ba2+-sensitive whole-cell current in MIN6 cell. These results suggest that TREK-2 contributes to the background K+ conductance in MIN6 cells, and may regulate depolarization-induced secretion of insulin.
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PMID:Functional expression of TREK-2 in insulin-secreting MIN6 cells. 1535 40