Mechanisms underlying regional differences in the Ca<sup>2+</sup>sensitivity of BK<sub>Ca</sub>current in arteriolar smooth muscle
Notice bibliographique
Résumé
Key points The plasma membrane large‐conductance Ca 2+ ‐activated, K + channel (BK Ca ) is a major ion channel contributing to the regulation of membrane potential. Activation of large‐conductance Ca 2+ ‐activated K + channel by both depolarization and increased intracellular Ca 2+ results in hyperpolarization that acts to limit agonist and mechanically induced vasoconstriction in small arteries. Using patch‐clamp techniques we demonstrate that regional differences exist in how BK Ca is regulated, particularly with respect to its Ca 2+ sensitivity. Using single‐channel recordings and siRNA to manipulate protein subunit expression, it is argued that the β1‐subunit plays a more dominant role in cerebral blood vessels as compared with small arteries from skeletal muscle. Subtle differences in the regulation of membrane potential in different vascular beds allow local blood flow and pressure to be closely adapted to the tissue's metabolic needs. Abstract β1‐Subunits enhance the gating properties of large‐conductance Ca 2+ ‐activated K + channels (BK Ca ) formed by α‐subunits. In arterial vascular smooth muscle cells (VSMCs), β1‐subunits are vital in coupling SR‐generated Ca 2+ sparks to BK Ca activation, affecting contractility and blood pressure. Studies in cremaster and cerebral VSMCs show heterogeneity of BK Ca activity due to apparent differences in the functional β1‐subunit:α‐subunit ratio. To define these differences, studies were conducted at the single‐channel level while siRNA was used to manipulate specific subunit expression. β1 modulation of the α‐subunit Ca 2+ sensitivity was studied using patch‐clamp techniques. BK Ca channel normalized open probability ( NP o ) versus membrane potential ( V m ) curves were more left‐shifted in cerebral versus cremaster VSMCs as cytoplasmic Ca 2+ was raised from 0.5 to 100 μ m . Calculated V 1/2 values of channel activation decreased from 72.0 ± 6.1 at 0.5 μ m Ca 2+ i to −89 ± 9 mV at 100 μ m Ca 2+ i in cerebral compared with 101 ± 10 to −63 ± 7 mV in cremaster VSMCs. Cremaster BK Ca channels thus demonstrated an ∼2.5‐fold weaker apparent Ca 2+ sensitivity such that at a value of V m of −30 mV, a mean value of [Ca 2+ ] i of 39 μ m was required to open half of the channels in cremaster versus 16 μ m [Ca 2+ ] i in cerebral VSMCs. Further, shortened mean open and longer mean closed times were evident in BK Ca channel events from cremaster VSMCs at either −30 or 30 mV at any given [Ca 2+ ]. β1‐Subunit‐directed siRNA decreased both the apparent Ca 2+ sensitivity of BK Ca in cerebral VSMCs and the appearance of spontaneous transient outward currents. The data are consistent with a higher ratio of β 1 ‐subunit:α‐subunit of BK Ca channels in cerebral compared with cremaster VSMCs. Functionally, this leads both to higher Ca 2+ sensitivity and NP o for BK Ca channels in the cerebral vasculature relative to that of skeletal muscle.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 ».