دورية أكاديمية
Loss of anoctamin 1 reveals a subtle role for BK channels in lymphatic muscle action potentials.
| العنوان: | Loss of anoctamin 1 reveals a subtle role for BK channels in lymphatic muscle action potentials. |
|---|---|
| المؤلفون: | Harlow RC; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA., Pea GA; Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, USA., Broyhill SE; Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, USA., Patro A; Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, USA., Bromert KH; Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, USA., Stewart RH; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA., Heaps CL; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA., Castorena-Gonzalez JA; Department of Pharmacology, Tulane University, New Orleans, LA, USA., Dongaonkar RM; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA., Zawieja SD; Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, USA. |
| المصدر: | The Journal of physiology [J Physiol] 2024 Jul; Vol. 602 (14), pp. 3351-3373. Date of Electronic Publication: 2024 May 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cambridge Univ. Press Country of Publication: England NLM ID: 0266262 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-7793 (Electronic) Linking ISSN: 00223751 NLM ISO Abbreviation: J Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Blackwell : Cambridge Univ. Press Original Publication: London, Cambridge Univ. Press. |
| مواضيع طبية MeSH: | Anoctamin-1*/metabolism , Anoctamin-1*/genetics , Large-Conductance Calcium-Activated Potassium Channels*/metabolism , Large-Conductance Calcium-Activated Potassium Channels*/physiology , Action Potentials*/physiology , Lymphatic Vessels*/physiology , Lymphatic Vessels*/metabolism, Animals ; Mice ; Rats ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle Contraction/physiology ; Rats, Sprague-Dawley ; Female ; Myocytes, Smooth Muscle/physiology ; Myocytes, Smooth Muscle/metabolism ; Myocytes, Smooth Muscle/drug effects |
| مستخلص: | Ca 2+ signalling plays a crucial role in determining lymphatic muscle cell excitability and contractility through its interaction with the Ca 2+ -activated Cl - channel anoctamin 1 (ANO1). In contrast, the large-conductance (BK) Ca 2+ -activated K + channel (KCa) and other KCa channels have prominent vasodilatory actions by hyperpolarizing vascular smooth muscle cells. Here, we assessed the expression and contribution of the KCa family to mouse and rat lymphatic collecting vessel contractile function. The BK channel was the only KCa channel consistently expressed in fluorescence-activated cell sorting-purified mouse lymphatic muscle cell lymphatic muscle cells. We used a pharmacological inhibitor of BK channels, iberiotoxin, and small-conductance Ca 2+ -activated K + channels, apamin, to inhibit KCa channels acutely in ex vivo isobaric myography experiments and intracellular membrane potential recordings. In basal conditions, BK channel inhibition had little to no effect on either mouse inguinal-axillary lymphatic vessel (MIALV) or rat mesenteric lymphatic vessel contractions or action potentials (APs). We also tested BK channel inhibition under loss of ANO1 either by genetic ablation (Myh11CreERT 2 -Ano1 fl/fl, Ano1ismKO) or by pharmacological inhibition with Ani9. In both Ano1ismKO MIALVs and Ani9-pretreated MIALVs, inhibition of BK channels increased contraction amplitude, increased peak AP and broadened the peak of the AP spike. In rat mesenteric lymphatic vessels, BK channel inhibition also abolished the characteristic post-spike notch, which was exaggerated with ANO1 inhibition, and significantly increased the peak potential and broadened the AP spike. We conclude that BK channels are present and functional on mouse and rat lymphatic muscle cells but are otherwise masked by the dominance of ANO1. KEY POINTS: Mouse and rat lymphatic muscle cells express functional BK channels. BK channels make little contribution to either rat or mouse lymphatic collecting vessel contractile function in basal conditions across a physiological pressure range. ANO1 limits the peak membrane potential achieved in the action potential and sets a plateau potential limiting the voltage-dependent activation of BK. BK channels are activated when ANO1 is absent or blocked and slightly impair contractile strength by reducing the peak membrane potential achieved in the action potential spike and accelerating the post-spike repolarization. (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.) |
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| معلومات مُعتمدة: | HL-168568 United States HL NHLBI NIH HHS; R00 HL141143 United States HL NHLBI NIH HHS; HL-143198 United States HL NHLBI NIH HHS; K99 HL141143 United States HL NHLBI NIH HHS; K99 HL143198 United States HL NHLBI NIH HHS; R00 HL143198 United States HL NHLBI NIH HHS; R01 HL168568 United States HL NHLBI NIH HHS; HL-141143 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: ANO1 channel; BK channel; action potential; lymphatics |
| المشرفين على المادة: | 0 (Anoctamin-1) 0 (Large-Conductance Calcium-Activated Potassium Channels) 0 (ANO1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240505 Date Completed: 20240715 Latest Revision: 20240718 |
| رمز التحديث: | 20240718 |
| مُعرف محوري في PubMed: | PMC11250503 |
| DOI: | 10.1113/JP285459 |
| PMID: | 38704841 |
| قاعدة البيانات: | MEDLINE |
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