Cardiac Electrophysiological Effects of Light-Activated Chloride Channels
Bibliographic record
Abstract
During the last decade, optogenetics has emerged as a paradigm-shifting technique to monitor and 18 steer the behavior of specific cell types in excitable tissues, including the heart. Activation of cation-19 conducting channelrhodopsins (ChR) leads to membrane depolarization, allowing one to effectively 20 trigger action potentials (AP) in cardiomyocytes. In contrast, the quest for optogenetic tools for 21 hyperpolarization-induced inhibition of AP generation has remained challenging. The green-light 22 activated ChR from Guillardia theta (GtACR1) mediates Cl--driven photocurrents that have been 23 shown to silence AP generation in different types of neurons. It has been suggested, therefore, to be a 24 suitable tool for inhibition of cardiomyocyte activity. Using single-cell electrophysiological 25 recordings and contraction tracking, as well as intracellular microelectrode recordings and in vivo 26 optical recordings of whole hearts, we find that GtACR1 activation by prolonged illumination arrests 27 cardiac cells in a depolarized state, thus inhibiting re-excitation. In line with this, GtACR1 activation 28 by transient light pulses elicits AP in isolated rabbit cardiomyocytes and in spontaneously beating 29 intact hearts of zebrafish. Our results show that GtACR1 inhibition of AP generation is caused by cell 30 depolarization. While this does not address the need for optogenetic silencing through physiological 31 means (i.e. hyperpolarization), GtACR1 is a potentially attractive tool for activating cardiomyocytes 32 by transient light-induced depolarization.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".