| id |
871e57a3-68f2-4548-99ff-a50346cef03e |
| user_id |
8684964a-bab1-4235-93a8-5fd5e24a1d0a |
| job_id |
jihzieju-0518 |
| base_model_name |
xevyo |
| base_model_path |
/home/sid/tuning/finetune/backend/output/xevyo-bas /home/sid/tuning/finetune/backend/output/xevyo-base-v1/merged_fp16_hf... |
| model_name |
Cardiac Contractility |
| model_desc |
Cardiac Contractility |
| model_path |
/home/sid/tuning/finetune/backend/output/jihzieju- /home/sid/tuning/finetune/backend/output/jihzieju-0518/merged_fp16_hf... |
| source_model_name |
xevyo |
| source_model_path |
/home/sid/tuning/finetune/backend/output/xevyo-bas /home/sid/tuning/finetune/backend/output/xevyo-base-v1/merged_fp16_hf... |
| source_job_id |
xevyo-base-v1 |
| dataset_desc |
The relationship between cardiac excitability and The relationship between cardiac excitability and contractility depends on when Ca2+
influx occurs during the ventricular action potential (AP). In mammals, it is accepted
that Ca2+ influx through the L-type Ca2+ channels occurs during AP phase 2.
However, in murine models, experimental evidence shows Ca2+ influx takes place
during phase 1. Interestingly, Ca2+ influx that activates contraction is highly regulated
by the autonomic nervous system. Indeed, autonomic regulation exerts multiple effects
on Ca2+ handling and cardiac electrophysiology. In this paper, we explore autonomic
regulation in endocardial and epicardial layers of intact beating mice hearts to evaluate
their role on cardiac excitability and contractility. We hypothesize that in mouse cardiac
ventricles the influx of Ca2+ that triggers excitation–contraction coupling (ECC) does
not occur during phase 2. Using pulsed local field fluorescence microscopy and loose
patch photolysis, we show sympathetic stimulation by isoproterenol increased the
amplitude of Ca2+ transients in both layers. This increase in contractility was driven
by an increase in amplitude and duration of the L-type Ca2+ current during phase 1.
Interestingly, the β-adrenergic increase of Ca2+ influx slowed the repolarization of
phase 1, suggesting a competition between Ca2+ and K+ currents during this phase.
In addition, cAMP activated L-type Ca2+ currents before SR Ca2+ release activated
the Na+-Ca2+ exchanger currents, indicating Cav1.2 channels are the initial target of
PKA phosphorylation. In contrast, parasympathetic stimulation by carbachol did not
have a substantial effect on amplitude and kinetics of endocardial and epicardial Ca2+
transients. However, carbachol transiently decreased the duration of the AP late phase 2
repolarization. The carbachol-induced shortening of phase 2 did not have a considerable
effect on ventricular pressure and systolic Ca2+ dynamics. Interestingly, blockade
of muscarinic receptors by atropine prolonged the duration of phase 2 indicating
that, in isolated hearts, there is an intrinsic release of acetylcholine. In addition, the
acceleration of repolarization induced by carbachol was blocked by the acetylcholine mediated K+ current inhibition. Our results reveal the transmural ramifications of
autonomic regulation in intact mice hearts and support our hypothesis that Ca2+ influx
that triggers ECC occurs in AP phase 1 and not in phase 2.
INTRODUCTION
MATERIALS AND METHODS
Heart Preparation
Pressure Recordings
Pulsed Local Field Fluorescence Microscopy
RNA Analysis
Electrical Recordings
Loose-Patch Photolysis
Statistical Analysis
RESULTS
All Figures
Cholinergic Stimulation Across the Ventricular Wall Did Not Alter Ca2+Dynamics
Cholinergic Stimulation Across the Ventricular Wall Was Mediated Via IKACh
Cholinergic Stimulation Modifies Endocardial and Epicardial Cardiac Excitability
CONCLUSION
ETHICS STATEMENT
AUTHOR CONTRIBUTIONS
SUPPLEMENTARY MATERIAL
FUNDING
ACKNOWLEDGMENTS
... |
| dataset_meta |
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| dataset_path |
/home/sid/tuning/finetune/backend/output/jihzieju- /home/sid/tuning/finetune/backend/output/jihzieju-0518/data/jihzieju-0518.json... |
| training_output |
null |
| status |
queued |
| created_at |
1769081401 |
| updated_at |
1769081932 |
| source_adapter_path |
NULL |
| adapter_path |
/home/sid/tuning/finetune/backend/output/jihzieju- /home/sid/tuning/finetune/backend/output/jihzieju-0518/adapter... |
| plugged_in |
False |