PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle Cells
PKC inhibitors stimulate Ca2+ release from internal stores in diverse cell types. Our data indicate that this action cannot be explained by an increased agonist-induced IP3 production or an overloaded SR Ca2+ pool in smooth muscle cells from guinea pig urinary bladder. The incubation of these cells...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.925023/full |
| _version_ | 1818244427810865152 |
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| author | Adan Dagnino-Acosta Agustín Guerrero-Hernandez |
| author_facet | Adan Dagnino-Acosta Agustín Guerrero-Hernandez |
| author_sort | Adan Dagnino-Acosta |
| collection | DOAJ |
| description | PKC inhibitors stimulate Ca2+ release from internal stores in diverse cell types. Our data indicate that this action cannot be explained by an increased agonist-induced IP3 production or an overloaded SR Ca2+ pool in smooth muscle cells from guinea pig urinary bladder. The incubation of these cells with three different PKC inhibitors, such as Go6976, Go6983, and BIM 1, resulted in a higher SR Ca2+ leak revealed by inhibition of the SERCA pump with thapsigargin. This SR Ca2+ leakage was sensitive to protein translocation inhibitors such as emetine and anisomycin. Since this increased SR Ca2+ leak did not result in a depleted SR Ca2+ store, we have inferred there was a compensatory increase in SERCA pump activity, resulting in a higher steady-state. This new steady-state increased the frequency of Spontaneous Transient Outward Currents (STOCs), which reflect the activation of high conductance, Ca2+-sensitive potassium channels in response to RyR-mediated Ca2+ sparks. This increased STOC frequency triggered by PKC inhibition was restored to normal by inhibiting translocon-mediated Ca2+ leak with emetine. These results suggest a critical role of PKC-mediated translocon phosphorylation in regulating SR Ca2+ steady-state, which, in turn, alters SR Ca2+ releasing activity. |
| first_indexed | 2024-12-12T14:16:51Z |
| format | Article |
| id | doaj.art-987c06224e9f41ea9faa393a16a53440 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-12T14:16:51Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-987c06224e9f41ea9faa393a16a534402022-12-22T00:21:53ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-06-011310.3389/fphys.2022.925023925023PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle CellsAdan Dagnino-Acosta0Agustín Guerrero-Hernandez1Centro Universitario de Investigaciones Biomédicas, CONACYT-Universidad de Colima, Colima, MexicoDepartamento de Bioquímica, Centro de Investigación y de Estudios Avanzados, Mexico City, MexicoPKC inhibitors stimulate Ca2+ release from internal stores in diverse cell types. Our data indicate that this action cannot be explained by an increased agonist-induced IP3 production or an overloaded SR Ca2+ pool in smooth muscle cells from guinea pig urinary bladder. The incubation of these cells with three different PKC inhibitors, such as Go6976, Go6983, and BIM 1, resulted in a higher SR Ca2+ leak revealed by inhibition of the SERCA pump with thapsigargin. This SR Ca2+ leakage was sensitive to protein translocation inhibitors such as emetine and anisomycin. Since this increased SR Ca2+ leak did not result in a depleted SR Ca2+ store, we have inferred there was a compensatory increase in SERCA pump activity, resulting in a higher steady-state. This new steady-state increased the frequency of Spontaneous Transient Outward Currents (STOCs), which reflect the activation of high conductance, Ca2+-sensitive potassium channels in response to RyR-mediated Ca2+ sparks. This increased STOC frequency triggered by PKC inhibition was restored to normal by inhibiting translocon-mediated Ca2+ leak with emetine. These results suggest a critical role of PKC-mediated translocon phosphorylation in regulating SR Ca2+ steady-state, which, in turn, alters SR Ca2+ releasing activity.https://www.frontiersin.org/articles/10.3389/fphys.2022.925023/fulltransloconPKCsarcoplasmic reticulumIP3smooth muscleSERCA |
| spellingShingle | Adan Dagnino-Acosta Agustín Guerrero-Hernandez PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle Cells Frontiers in Physiology translocon PKC sarcoplasmic reticulum IP3 smooth muscle SERCA |
| title | PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle Cells |
| title_full | PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle Cells |
| title_fullStr | PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle Cells |
| title_full_unstemmed | PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle Cells |
| title_short | PKC Inhibits Sec61 Translocon-Mediated Sarcoplasmic Reticulum Ca2+ Leak in Smooth Muscle Cells |
| title_sort | pkc inhibits sec61 translocon mediated sarcoplasmic reticulum ca2 leak in smooth muscle cells |
| topic | translocon PKC sarcoplasmic reticulum IP3 smooth muscle SERCA |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.925023/full |
| work_keys_str_mv | AT adandagninoacosta pkcinhibitssec61transloconmediatedsarcoplasmicreticulumca2leakinsmoothmusclecells AT agustinguerrerohernandez pkcinhibitssec61transloconmediatedsarcoplasmicreticulumca2leakinsmoothmusclecells |