Ca2+ microdomain-based excitation-transcription coupling in cardiac myocytes and vascular smooth muscle cells
Bibliographic record
Abstract
Abstract Ca2+ signals play a crucial role in maintaining cardiovascular homeostasis, including regulation of the heartbeat, blood pressure, and adaptation to changes in the external environment. Conversely, abnormal Ca2+ signaling is often involved in the onset and progression of cardiovascular diseases, such as cardiac hypertrophy, heart failure, arteriosclerosis, and hypertension. In excitable cells, such as cardiac myocytes and vascular smooth muscle cells (VSMCs), membrane depolarization, and the subsequent elevation of cytosolic Ca2+ concentration ([Ca2+]cyt) via voltage-dependent Ca2+ channels (VDCCs) cause muscle contraction, which is known as excitation–contraction coupling (E-C coupling). Elevated [Ca2+]cyt can also activate Ca2+-dependent enzymes, in some cases leading to changes in gene expression patterns and contributing to long-term cellular responses. This mechanism is referred to as excitation-transcription coupling (E-T coupling), and it is involved in both the adaptive and pathological responses of the cardiovascular system to chronic stimulation. Specific intracellular regions, known as Ca2+ microdomains, exhibit localized increases in [Ca2+]cyt. Such localized Ca2+ signaling is now known to be one of the molecular mechanisms controlling the diversity of Ca2+ responses. These Ca2+ microdomains are often formed by complexes consisting of Ca2+ channels and downstream Ca2+-dependent enzymes localized by scaffolding proteins. This review outlines some of the molecular mechanisms and roles of Ca2+ microdomain-based E-T coupling in cardiac myocytes and VSMCs. First, we discuss the major molecular components that are essential for functional Ca2+ microdomains. For example, VDCC (CaV1.2 channel), ryanodine receptor (RyR), Ca2+-dependent enzymes (Ca2+/CaM-dependent kinase [CaMK], calcineurin [CaN], and calpain), and scaffolding proteins (A-kinase anchoring proteins [AKAPs], caveolin, and junctophilin). Next, we discuss the roles of Ca2+ microdomain-based E-T coupling in physiological and pathophysiological remodeling in cardiac myocytes and vascular smooth muscle cells.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".