Identification of a new splice variant of large‐conductance Ca <sup>2+</sup> ‐activated K <sup>+</sup> (BK) channel α subunit from human chondrocyte
Bibliographic record
Abstract
Changes in intracellular calcium concentration ([Ca 2+ ] i ) modulate chondrogenesis, proliferation, cell death and baseline anabolic and catabolic activities in chondrocytes. Under pathophysiological conditions, like osteoarthritis (OA), histamine release from resident mast cells enhances the production of pro‐inflammatory mediators and the activities of matrix degrading enzymes. Specific patterns of [Ca 2+ ] i changes are considered as essential components initiating and/or progressing the disease. In an established model cell‐line of the human chondrocyte, OUMS‐27 cells, large‐conductance Ca 2+ ‐activated K + (BK) channels are involved in the enhancement of histamine‐induced Ca 2+ influx by the activation of Ca 2+ release‐activated Ca 2+ (CRAC) channels consisting of Orai1‐Orai2 heteromers and STIM1 via the modulation of membrane potential. We have identified a novel BKα splice variant (BKαΔe2) in OUMS‐27 cells. Although BKαΔe2 lacks exon2 that codes the intracellular S0–S1 linker (Glu127‐Leu180), significant expression was detected in several human tissues including chondrocytes of OA patients and in mouse tissues as well. BKαΔe2 channels are not expressed on plasma membrane (PM), but can traffic to PM after forming hetero‐tetramer units with wild‐type BKα (BKαWT). These hetero‐tetramers of BKα have a smaller single channel conductance and exhibit lower trafficking efficiency than BKαWT homo‐tetramers in a stoichiometry‐dependent manner. BKαΔe2 knockdown in OUMS‐27 chondrocytes increased BK current density, and augmented the responsiveness to histamine assayed as cyclooxygenase‐2 gene expression. These findings provide significant new evidence that BKαΔe2 can modulate cellular responses to physiological stimuli in human chondrocyte and contribute under pathophysiological conditions, such as OA. Support or Funding Information This work was supported by JSPS KAKENHI Grant Numbers, 26293021 and 15H01408 to Y.I., 26860059, 16H06215 and 16K15127 to Y.S., 16K08278 to H.Y. This work was also supported by a Grant‐in‐Aid from Takeda Science Foundation (to Y.S.) and Salt Science Research Foundation [Grant 1637] (to Y.S.). W.G. holds an Alberta Innovates‐Health Solutions Scientist Award, and CIHR funding. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".