Distinct roles of L‐ and T‐type voltage‐dependent Ca<sup>2+</sup>channels in regulation of lymphatic vessel contractile activity
Notice bibliographique
Résumé
Key points Lymph transport is promoted by lymphatic pumping, a robust phasic contractile activity of the collecting lymphatic vessels. This contractile function, critical for tissue fluid homeostasis and immune cell transport to lymph nodes, is regulated by the amount of lymph entering the vessels and subsequent distension of the vessel wall. While lymphatic pumping relies on influx of Ca 2+ through voltage‐dependent Ca 2+ channels, characterization of these channels and details of their contribution to the regulation of stretch‐activated contractions are lacking. Here we report the expression of L‐ and T‐type Ca 2+ channels in rat mesenteric lymphatic vessels and their differential role in regulating strength and frequency of lymphatic contractions. This study fosters our knowledge on the mechanisms that drive stretch‐activated lymphatic contractions. It may help in providing a basis to developing agents able to enhance lymphatic function, which could be of therapeutic benefit during lymphatic impairment such as lymphoedema. Abstract Lymph drainage maintains tissue fluid homeostasis and facilitates immune response. It is promoted by phasic contractions of collecting lymphatic vessels through which lymph is propelled back into the blood circulation. This rhythmic contractile activity (i.e. lymphatic pumping) increases in rate with increase in luminal pressure and relies on activation of nifedipine‐sensitive voltage‐dependent Ca 2+ channels (VDCCs). Despite their importance, these channels have not been characterized in lymphatic vessels. We used pressure‐ and wire‐myography as well as intracellular microelectrode electrophysiology to characterize the pharmacological and electrophysiological properties of L‐type and T‐type VDCCs in rat mesenteric lymphatic vessels and evaluated their particular role in the regulation of lymphatic pumping by stretch. We complemented our study with PCR and confocal immunofluorescence imaging to investigate the expression and localization of these channels in lymphatic vessels. Our data suggest a delineating role of VDCCs in stretch‐induced lymphatic vessel contractions, as the stretch‐induced increase in force of lymphatic vessel contractions was significantly attenuated in the presence of L‐type VDCC blockers nifedipine and diltiazem, while the stretch‐induced increase in contraction frequency was significantly decreased by the T‐type VDCC blockers mibefradil and nickel. The latter effect was correlated with a hyperpolarization. We propose that activation of T‐type VDCCs depolarizes membrane potential, regulating the frequency of lymphatic contractions via opening of L‐type VDCCs, which drive the strength of contractions.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».