Regulation of Proliferation and Membrane Potential by Chloride Currents in Rat Pulmonary Artery Smooth Muscle Cells
Bibliographic record
Abstract
Pulmonary artery smooth muscle cell (PASMC) proliferation contributes to increased pulmonary vascular resistance and pulmonary hypertension. Because proliferation depends on membrane potential (V(m)) and because V(m) is, in part, determined by Cl(-) currents (I(Cl)), we examined the effects of I(Cl) inhibition with 4,4;-diisothiocyanatostilbene-2,2;-disulfonic acid (DIDS) on cultured rat PASMCs. DIDS (30 mumol/L) reduced cell numbers, decreased 5-bromodeoxyuridine incorporation and delayed cell cycle progression. I(Cl) inhibition with 5-Nitro-2-(3-phenylpropylamino) benzoic acid (100 mumol/L) also reduced cell numbers of cultured rat PASMCs. To test the possible involvement of I(Cl) in the regulation of PASMC proliferation, we measured V(m) and I(Cl) in both cultured (proliferating) and acutely dissociated (nonproliferating) rat PASMCs. V(m) (-39.3+/-1.4 mV) was close to the equilibrium potential of Cl(-) (-39 mV) in proliferating PASMCs but differed from equilibrium potential of Cl(-) in acutely dissociated cells (-45.3+/-0.9 mV). DIDS and substitution of extracellular Cl(-) with I(-) induced V(m) hyperpolarization in proliferating but not nonproliferating PASMCs. Consistent with V(m) recordings, DIDS-sensitive baseline and swelling-activated (Ca(2+)-independent) I(Cl)s, recorded with low Ca(2+) (<1 nmol/L) pipette solutions, were approximately 5-fold greater in proliferating than in nonproliferating PASMCs. By contrast, Ca(2+)-activated I(Cl) did not differ between proliferating and nonproliferating PASMCs. Ca(2+)-independent I(Cl)s were also increased in proliferating PASMCs acutely dissociated from rats exposed to hypoxia (10% O(2); 7 days). These findings are consistent with the conclusion that I(Cl)s regulate proliferation of PASMCs and suggest that selective I(Cl) inhibition may be useful in treating pulmonary hypertension.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 0.000 |
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 teacher head, 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".