Abstract 12087: KCa3.1 Channels Support Resting Potential and Proliferative Function During Store-Operated Ca <sup>2+</sup> -Entry in c-kit <sup>+</sup> Endogenous Cardiac Stem Cells
Bibliographic record
Abstract
Introduction: Adult hearts contain c-kit + endogenous cardiac stem cells (eCSCs). Cultured eCSCs express a wide range of ion channels, but cell culture is known to affect phenotype. Here we defined ion currents in freshly isolated c-kit + eCSCs and their potential functional role. Methods: eCSCs isolated from healthy and heart failure (HF, ventricular tachypacing X 2 wks) dog hearts were magnetically purified with c-kit antibodies. Ion currents and membrane potential were recorded with patch clamp. Results: Contrary to cultured c-kit + eCSCs, ion currents were barely detectable with Ca 2+ i buffered (Fig A). Free Ca 2+ i activated prominent I KCa3.1 (TRAM34 sensitive, Fig B) in 82% of cells. I KCa3.1 was reduced in eCSCs isolated from HF dogs (Fig C), along with corresponding KCNN4 mRNA (Fig D). Under perforated patch to maintain spontaneous physiological [Ca 2+ ] i , eCSCs had a membrane potential (V mem ) of -73±10 mV. Ca 2+ i depletion with nominally 0 mM [Ca 2+ ] o strongly depolarized the membrane. After passive Ca 2+ i depletion, store-operated channel (SOC) mediated Ca 2+ entry (SOCE) caused a robust V mem hyperpolarization (from -21±4 to -79±7 mV, p<0.001). The SOCE effect on V mem was substantially reduced by both 2-APB (SOC inhibitor) and TRAM34 (Fig E). Inhibiting KCa3.1 (TRAM34, 0.1 μM) or SOCs (2-APB, 50 μM) in culture decreased c-kit + eCSCs proliferation by 21% (p<0.05) and 55% (p<0.001) respectively. Conclusions: In contrast to cultured eCSCs, voltage-dependent ion currents are virtually absent from freshly isolated c-kit + eCSCs. I KCa3.1 is prominent and maintains V mem in the face of substantial Ca 2+ entry from SOCs. This Ca 2+ entry would normally depolarize the cell, reduce the gradient for Ca 2+ entry and turn off the Ca 2+ signal. We hypothesize that the Ca 2+ -mediated KCa3.1 K + -conductance increase is necessary to maintain V mem in the face of the Ca 2+ entry that activates eCSC proliferation, and that KCa3.1 channels may therefore play an important role in eCSC function.
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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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".