Apelin-13 Inhibits Large-Conductance Ca2+-Activated K+ Channels in Cerebral Artery Smooth Muscle Cells via a PI3-Kinase Dependent Mechanism
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{"title"=>"Apelin-13 Inhibits Large-Conductance Ca2+-Activated K+ Channels in Cerebral Artery Smooth Muscle Cells via a PI3-Kinase Dependent Mechanism", "type"=>"journal", "authors"=>[{"first_name"=>"Amit", "last_name"=>"Modgil"}, {"first_name"=>"Lirong", "last_name"=>"Guo"}, {"first_name"=>"Stephen T.", "last_name"=>"O’Rourke"}, {"first_name"=>"Chengwen", "last_name"=>"Sun"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"1932-6203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0083051", "pmid"=>"24386141"}, "id"=>"0bc597a3-54e0-3db3-b42f-eb2c0007160f", "abstract"=>"Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle (VSM) cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca(2+)-activated K(+) (BKCa) channels in VSM cells are critical regulators of membrane potential and vascular tone. In the present study, we examined the effect of apelin-13 on BKCa channel activity in VSM cells, freshly isolated from rat middle cerebral arteries. In whole-cell patch clamp mode, apelin-13 (0.001-1 μM) caused concentration-dependent inhibition of BKCa in VSM cells. Apelin-13 (0.1 µM) significantly decreased BKCa current density from 71.25±8.14 pA/pF to 44.52±7.10 pA/pF (n=14 cells, P<0.05). This inhibitory effect of apelin-13 was confirmed by single channel recording in cell-attached patches, in which extracellular application of apelin-13 (0.1 µM) decreased the open-state probability (NPo) of BKCa channels in freshly isolated VSM cells. However, in inside-out patches, extracellular application of apelin-13 (0.1µM) did not alter the NPo of BKCa channels, suggesting that the inhibitory effect of apelin-13 on BKCa is not mediated by a direct action on BKCa. In whole cell patches, pretreatment of VSM cells with LY-294002, a PI3-kinase inhibitor, markedly attenuated the apelin-13-induced decrease in BKCa current density. In addition, treatment of arteries with apelin-13 (0.1 µM) significantly increased the ratio of phosphorylated-Akt/total Akt, indicating that apelin-13 significantly increases PI3-kinase activity. Taken together, the data suggest that apelin-13 inhibits BKCa channel via a PI3-kinase-dependent signaling pathway in cerebral artery VSM cells, which may contribute to its regulatory action in the control of vascular tone.", "link"=>"http://www.mendeley.com/research/apelin13-inhibits-largeconductance-ca2activated-k-channels-cerebral-artery-smooth-muscle-cells-via-p", "reader_count"=>8, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>3, "Biochemistry, Genetics and Molecular Biology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1328895"], "description"=>"<p>Phosphorylated AKT and total AKT were measured in cerebral arteries treated with apelin-13 (0.1 µM) or apelin-13 plus LY-294002 (LY, 10 µM) for durations indicated in the figure. <b>A</b>: The represented blots were probed with anti serine-phosphorylation of Akt (pAkt) or anti-Akt (total) antibodies. <b>B</b>: Bar graphs summarizing the effect of apelin-13 on PI3-kinase activity expressed as a ratio of p-Akt/Akt protein levels. Data are means ± SEM derived from three independent experiments. *P<0.05 compared with non-stimulated control.</p>", "links"=>[], "tags"=>["apelin-13", "pi3-kinase", "cerebral", "arteries", "blot"], "article_id"=>886846, "categories"=>["Biological Sciences"], "users"=>["Amit Modgil", "Lirong Guo", "Stephen T. O’Rourke", "Chengwen Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083051.g006", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_apelin_13_on_PI3_kinase_activity_measured_in_rat_cerebral_arteries_using_western_blot_as_described_in_the_Methods_/886846", "title"=>"Effect of apelin-13 on PI3-kinase activity measured in rat cerebral arteries using western blot as described in the Methods.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:09:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1328892"], "description"=>"<p>Currents were recorded at room temperature with a pipette potential of -40 mV. <b>A</b>: Representative tracings showing the large-conductance K<sup>+</sup> channel currents recorded from cell-attached patches of VSM cells under the following sequential treatment conditions: Control; apelin-13 (0.1 µM, 5 min); washout. <b>B</b>: Bar graph summarizing the open state probability (NP<sub>o</sub>) of BK<sub>Ca</sub> channels during each treatment condition described above. *<i>P</i><0.05 indicates a significant difference from the corresponding control value. Values presented are mean±SEM recorded from 9 cells. </p>", "links"=>[], "tags"=>["apelin-13", "channels", "recorded", "cell-attached", "patches", "cerebral", "arterial", "vsm"], "article_id"=>886843, "categories"=>["Biological Sciences"], "users"=>["Amit Modgil", "Lirong Guo", "Stephen T. O’Rourke", "Chengwen Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083051.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_apelin_13_on_the_activity_of_BK_Ca_channels_recorded_from_cell_attached_patches_of_rat_middle_cerebral_arterial_VSM_cells_/886843", "title"=>"Effects of apelin-13 on the activity of BK<sub>Ca</sub> channels recorded from cell-attached patches of rat middle cerebral arterial VSM cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:09:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1328891"], "description"=>"<p>Whole-cell BK<sub>Ca</sub> currents were recorded in rat middle cerebral arterial VSM cells as described in the Methods. <b>A</b>-<b>D</b>: representative tracings depicting the currents recorded from a single VSM cell under the following sequential treatment conditions: Control (A), followed by superfusion with apelin-13 (0.1 µM, 5 min) (B), washout of apelin-13, superfusion with Pertussis toxin (PT, 100 nM, 5 min) (C), and superfusion with apelin-13 plus Pertussis toxin (D). <b>E</b>: Average whole-cell current-voltage plots of BK<sub>Ca</sub> current. <b>F</b>: Bar graphs summarizing the average current density (pA/pF) at +50 mV obtained at each treatment condition described above. Values are mean±SEM (n=6). *<i>P</i><0.05 indicates a significant difference from the corresponding control value.</p>", "links"=>[], "tags"=>["pertussis", "toxin", "apelin-13", "channels", "cerebral", "arterial", "vsm"], "article_id"=>886842, "categories"=>["Biological Sciences"], "users"=>["Amit Modgil", "Lirong Guo", "Stephen T. O’Rourke", "Chengwen Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083051.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_pertussis_toxin_and_apelin_13_on_BK_Ca_channels_in_rat_middle_cerebral_arterial_VSM_cells_/886842", "title"=>"Effect of pertussis toxin and apelin-13 on BK<sub>Ca</sub> channels in rat middle cerebral arterial VSM cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:09:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1328894"], "description"=>"<p>Whole-cell BK<sub>Ca</sub> currents were recorded as described in the Methods. <b>A</b>-<b>D</b>: Representative tracings showing the currents recorded from a single VSM cell under the following sequential treatment conditions: control (A); followed by superfusion with 0.1 µM apelin-13 (B) for 5 min; washout of apelin-13; superfusion with LY-294002 (10 mM, 5 min) (C); and superfusion with apelin-13 plus LY-294002 (D). <b>E</b>: Average whole cell current density-voltage plots of BK<sub>ca</sub> current. <b>F</b>: Bar graph summarizing the average current density (pA/pF) at 50 mV obtained at each treatment condition described above. Values are mean±SEM (n=6 cells). *<i>P</i><0.05 indicates a significant difference from the corresponding control value.</p>", "links"=>[], "tags"=>["pi3-kinase", "inhibition", "inhibitory", "apelin-13", "currents", "cerebral", "arterial", "vsm"], "article_id"=>886845, "categories"=>["Biological Sciences"], "users"=>["Amit Modgil", "Lirong Guo", "Stephen T. O’Rourke", "Chengwen Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083051.g005", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_PI3_kinase_inhibition_on_the_inhibitory_action_of_apelin_13_on_BK_Ca_channel_currents_in_rat_middle_cerebral_arterial_VSM_cells_/886845", "title"=>"Effect of PI3-kinase inhibition on the inhibitory action of apelin-13 on BK<sub>Ca</sub> channel currents in rat middle cerebral arterial VSM cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:09:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1328893"], "description"=>"<p>Currents were recorded at room temperature before and after administration of apelin-13 through the recording pipettes. <b>A</b>: Representative tracings depicting the effects of apelin-13 (0.1 µM, 5 min) on the large-conductance K<sup>+</sup> channel currents recorded from inside-out patches of VSM cells isolated from rat middle cerebral arteries. <b>B</b>: Bar graph summarizing the open state probability (NP<sub>o</sub>) of BK<sub>Ca</sub> channels before and after administration of apelin-13 (0.1 µM). Values presented are mean±SEM recorded from 7 cells.</p>", "links"=>[], "tags"=>["apelin-13", "recorded", "inside-out", "patches", "vsm", "cells", "freshly", "cerebral"], "article_id"=>886844, "categories"=>["Biological Sciences"], "users"=>["Amit Modgil", "Lirong Guo", "Stephen T. O’Rourke", "Chengwen Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083051.g004", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_apelin_13_on_BK_Ca_channel_activity_recorded_from_inside_out_patches_of_VSM_cells_freshly_isolated_from_rat_middle_cerebral_arteries_/886844", "title"=>"Effect of apelin-13 on BK<sub>Ca</sub> channel activity recorded from inside-out patches of VSM cells freshly isolated from rat middle cerebral arteries.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:09:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1328890"], "description"=>"<p>Whole-cell K<sup>+</sup> currents were recorded at room temperature in response to successive voltage pulses of 800 ms duration, increasing in 10-mV increments from -70 mV to +50 mV before and after the treatment of apelin-13 (0.001-1 µM). <b>A</b>-<b>D</b>: representative tracings depicting the currents recorded from a single VSM cell before and after treatment with apelin-13 (0.1 µM, 5 min) or iberiotoxin (IBT) (100 nM, 5 min). <b>E</b>: I-V curve plots of BK<sub>Ca</sub> currents at baseline and after application of apelin-13 (0.1 µM, 5 min). <b>F</b>: Bar graph summarizing the concentration-dependent effect of apelin-13 (0.001-1 µM) on average current density (pA/pF) at +50 mV. Values are mean±SEM (n=6 to 14 cells). *<i>P</i><0.05 indicates a significant difference from the corresponding control value. <b>G</b>: A representative VSM cell isolated from rat middle cerebral arteries under optical phase and fluorescence imaging. Fluorescence micrographs demonstrate the APJ receptor expression in VSM cells immunostained with anti-alpha smooth muscle actin antibodies (red) and anti-APJ receptor antibodies (green). The overlap of these two images shows that green fluorescence is VSM cell-located. </p>", "links"=>[], "tags"=>["apelin-13", "conductance", "channels", "cerebral", "arterial", "vsm"], "article_id"=>886841, "categories"=>["Biological Sciences"], "users"=>["Amit Modgil", "Lirong Guo", "Stephen T. O’Rourke", "Chengwen Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0083051.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_apelin_13_on_activity_of_large_conductance_Ca_2_activated_K_BK_Ca_channels_of_rat_middle_cerebral_arterial_VSM_cells_/886841", "title"=>"Effect of apelin-13 on activity of large conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK<sub>Ca</sub> ) channels of rat middle cerebral arterial VSM cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:09:01"}

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  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Biology and life sciences/Biophysics", "average_usage"=>[256, 434, 551, 657, 750, 827, 909, 1003, 1078, 1136, 1201, 1279, 1323]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[262, 463, 587, 693, 790, 882, 965, 1051, 1135, 1218, 1300, 1376, 1438]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[258, 449, 572, 679, 775, 866, 956, 1041, 1124, 1211, 1291, 1371, 1437]}, {"subject_area"=>"/Physical sciences/Physics", "average_usage"=>[254, 421, 527, 626, 720, 813, 900, 983, 1063, 1136, 1210, 1283, 1342]}]}
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