Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> Channels
Opening of large conductance calcium-activated and voltage-dependent potassium (BK<sub>Ca</sub>) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H<...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/11/1127 |
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| author | Yan Li Jin Bai Yi-hua Yang Naoto Hoshi Dong-bao Chen |
| author_facet | Yan Li Jin Bai Yi-hua Yang Naoto Hoshi Dong-bao Chen |
| author_sort | Yan Li |
| collection | DOAJ |
| description | Opening of large conductance calcium-activated and voltage-dependent potassium (BK<sub>Ca</sub>) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H<sub>2</sub>S) has been recently identified as a new UA vasodilator, yet the mechanism underlying H<sub>2</sub>S-induced UA dilation is unknown. Here, we tested whether H<sub>2</sub>S activated BK<sub>Ca</sub> channels in human UA smooth muscle cells (hUASMC) to mediate UA relaxation. Multiple BK<sub>Ca</sub> subunits were found in human UA in vitro and hUASMC in vitro, and high β1 and γ1 proteins were localized in SM cells in human UA. Baseline outward currents, recorded by whole-cell and single-channel patch clamps, were significantly inhibited by specific BK<sub>Ca</sub> blockers iberiotoxin (IBTX) or tetraethylammonium, showing specific BK<sub>Ca</sub> activity in hUASMC. H<sub>2</sub>S dose (NaHS, 1–1000 µM)-dependently potentiated BK<sub>Ca</sub> currents and open probability. Co-incubation with a Ca<sup>2+</sup> blocker nifedipine (5 µM) or a chelator (ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), 5 mM) did not alter H<sub>2</sub>S-potentiated BK<sub>Ca</sub> currents and open probability. NaHS also dose-dependently relaxed phenylephrine pre-constricted freshly prepared human UA rings, which was inhibited by IBTX. Thus, H<sub>2</sub>S stimulated human UA relaxation at least partially via activating SM BK<sub>Ca</sub> channels independent of extracellular Ca<sup>2+</sup>. |
| first_indexed | 2024-03-10T14:51:50Z |
| format | Article |
| id | doaj.art-6edbc1d9692946769a71cf3a901b884a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T14:51:50Z |
| publishDate | 2020-11-01 |
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| series | Antioxidants |
| spelling | doaj.art-6edbc1d9692946769a71cf3a901b884a2023-11-20T20:53:45ZengMDPI AGAntioxidants2076-39212020-11-01911112710.3390/antiox9111127Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> ChannelsYan Li0Jin Bai1Yi-hua Yang2Naoto Hoshi3Dong-bao Chen4Department of Obstetrics & Gynecology, University of California, Irvine, CA 92697, USADepartment of Obstetrics & Gynecology, University of California, Irvine, CA 92697, USADepartment of Obstetrics & Gynecology, University of California, Irvine, CA 92697, USADepartment of Pharmacology, University of California, Irvine, CA 92697, USADepartment of Obstetrics & Gynecology, University of California, Irvine, CA 92697, USAOpening of large conductance calcium-activated and voltage-dependent potassium (BK<sub>Ca</sub>) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H<sub>2</sub>S) has been recently identified as a new UA vasodilator, yet the mechanism underlying H<sub>2</sub>S-induced UA dilation is unknown. Here, we tested whether H<sub>2</sub>S activated BK<sub>Ca</sub> channels in human UA smooth muscle cells (hUASMC) to mediate UA relaxation. Multiple BK<sub>Ca</sub> subunits were found in human UA in vitro and hUASMC in vitro, and high β1 and γ1 proteins were localized in SM cells in human UA. Baseline outward currents, recorded by whole-cell and single-channel patch clamps, were significantly inhibited by specific BK<sub>Ca</sub> blockers iberiotoxin (IBTX) or tetraethylammonium, showing specific BK<sub>Ca</sub> activity in hUASMC. H<sub>2</sub>S dose (NaHS, 1–1000 µM)-dependently potentiated BK<sub>Ca</sub> currents and open probability. Co-incubation with a Ca<sup>2+</sup> blocker nifedipine (5 µM) or a chelator (ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), 5 mM) did not alter H<sub>2</sub>S-potentiated BK<sub>Ca</sub> currents and open probability. NaHS also dose-dependently relaxed phenylephrine pre-constricted freshly prepared human UA rings, which was inhibited by IBTX. Thus, H<sub>2</sub>S stimulated human UA relaxation at least partially via activating SM BK<sub>Ca</sub> channels independent of extracellular Ca<sup>2+</sup>.https://www.mdpi.com/2076-3921/9/11/1127hydrogen sulfideBK<sub>Ca</sub> channelssmooth muscleuterine arterywomen |
| spellingShingle | Yan Li Jin Bai Yi-hua Yang Naoto Hoshi Dong-bao Chen Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> Channels Antioxidants hydrogen sulfide BK<sub>Ca</sub> channels smooth muscle uterine artery women |
| title | Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> Channels |
| title_full | Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> Channels |
| title_fullStr | Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> Channels |
| title_full_unstemmed | Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> Channels |
| title_short | Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BK<sub>Ca</sub> Channels |
| title_sort | hydrogen sulfide relaxes human uterine artery via activating smooth muscle bk sub ca sub channels |
| topic | hydrogen sulfide BK<sub>Ca</sub> channels smooth muscle uterine artery women |
| url | https://www.mdpi.com/2076-3921/9/11/1127 |
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