Modulation of the human polycystin‐L channel by voltage and divalent cations
Bibliographic record
Abstract
Polycystin-L (PCL) is highly homologous in sequence and membrane topology to polycystin-2, the product of the second gene responsible for autosomal dominant polycystic kidney disease (ADPKD). PCL and polycystin-2 were recently shown to be Ca2+-permeable, Ca2+-activated cation channels. Further characterization of polycystins will help in the understanding of cystogenesis and pathogenesis of ADPKD. In the present study, we expressed human PCL in Xenopus oocytes and studied its function utilizing patch-clamp and two-electrode voltage clamp techniques. In addition to its permeability to Ca2+, K+ and Na+, PCL was highly permeable to NH4+ and Cs+ with a permeability ratio NH4+:Cs+:Na+ of 2.2:1.02:1. Voltage modulation of channel properties was studied using cell-attached (C-A) and excised inside-out (I-O) patches. In the C-A mode, the open probability (NP(o)) of PCL at negative potentials (NP(o)=0.22) was higher than at positive potentials (NP(o)=0.05). The mean open time averaged 31.6 ms at negative potentials, and 6.2 ms at positive potentials; single-channel activity exhibited bursts with a mean interburst time of 178 ms. Using I-O patches under symmetrical ionic conditions, single-channel inward conductance was significantly larger than outward conductance, indicating a slight inward rectification. External Mg2+ inhibited the PCL channel currents. The inhibitory effect was voltage-dependent and substantially reduced by depolarization. The time course of inactivation depended on external calcium concentration but was independent of voltage and peak current. This study shows that although PCL is not a voltage-gated channel, its channel activity and inhibition by Mg2+ are modulated by membrane potential.
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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".