{"id":{"repo_id":"kings","oai_identifier":"oai:kclpure.kcl.ac.uk:studenttheses/0754e26d-374a-485e-9387-41e074926048"},"canonical_url":"https://search.dev.ndltd.org/etd/kings/oai:kclpure.kcl.ac.uk:studenttheses/0754e26d-374a-485e-9387-41e074926048","repository":{"repo_id":"kings","name":"King's College London","base_url":"https://kclpure.kcl.ac.uk/ws/oai"},"display":{"title":"Studies of calcium signalling mechanisms in human platelets","abstract":"Platelet activation is essential in haemostasis and thrombosis and central to this role is cytosolic calcium (Ca2+) elevation. The two ways in which this can occur are release from intracellular Ca2+ stores and the entry of Ca2+ across the plasma membrane (PM). Changes in cytosolic Ca2+ are required to enable a variety of platelet responses. In platelets and other non-excitable cells, the major route of Ca2+ entry occurs as a result of Ca2+ depletion from intracellular stores, and is known as store operated Ca2+ entry (SOCE). STIM1 is the Ca2+ sensing protein of the endoplasmic reticulum (ER) which activates Orai channels in the plasma membrane allowing Ca + entry. However, not all of the details of Ca2+ entry are understood. In platelets, two other pathways also enable Ca2+ entry. The P2X1 receptor is a ligand gated ion channel activated by the binding of ATP. Second messengers (such as 1,2-diacyl-sn- glycerol [DAG]) and phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) may directly gate plasma membrane cation channels such as the transient receptor potential canonical 6 (TRPC6) channel. -- The main aim of this study was to examine the role of STIM1 and TRPC proteins in Ca2+ entry in human platelets. The TRPC1 protein was originally proposed to be a major component of the SOC channel based on the observation that a commercial preparation of an anti-TRPCl antibody against the channel impaired SOCE in platelets. However, in the current study I demonstrate the failure of this reagent to bind to TRPC1. The previously reported inhibitory effect on SOCE may be due in part to be a result of the azide component of the antibody preparation.","abstract_html":"Platelet activation is essential in haemostasis and thrombosis and central to this role is cytosolic calcium (Ca2+) elevation. The two ways in which this can occur are release from intracellular Ca2+ stores and the entry of Ca2+ across the plasma membrane (PM). Changes in cytosolic Ca2+ are required to enable a variety of platelet responses. In platelets and other non-excitable cells, the major route of Ca2+ entry occurs as a result of Ca2+ depletion from intracellular stores, and is known as store operated Ca2+ entry (SOCE). STIM1 is the Ca2+ sensing protein of the endoplasmic reticulum (ER) which activates Orai channels in the plasma membrane allowing Ca + entry. However, not all of the details of Ca2+ entry are understood. In platelets, two other pathways also enable Ca2+ entry. The P2X1 receptor is a ligand gated ion channel activated by the binding of ATP. Second messengers (such as 1,2-diacyl-sn- glycerol [DAG]) and phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) may directly gate plasma membrane cation channels such as the transient receptor potential canonical 6 (TRPC6) channel. -- The main aim of this study was to examine the role of STIM1 and TRPC proteins in Ca2+ entry in human platelets. The TRPC1 protein was originally proposed to be a major component of the SOC channel based on the observation that a commercial preparation of an anti-TRPCl antibody against the channel impaired SOCE in platelets. However, in the current study I demonstrate the failure of this reagent to bind to TRPC1. The previously reported inhibitory effect on SOCE may be due in part to be a result of the azide component of the antibody preparation.","abstract_has_math":false,"creators":["Ambily, Anju"],"institution":"King's College London","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Authi, Kalwant Singh","Pearson, Jeremy David"],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012","date_published":"2012","updated_at":"2026-07-24T02:44:31Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/0754e26d-374a-485e-9387-41e074926048"],"render_values":[{"text":"oai:kclpure.kcl.ac.uk:studenttheses/0754e26d-374a-485e-9387-41e074926048","href":null,"code":true}]}]},"links":{"outbound_url":"https://kclpure.kcl.ac.uk/portal/en/studentTheses/0754e26d-374a-485e-9387-41e074926048","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Authi, Kalwant Singh","Pearson, Jeremy David"]},{"key":"dc:creator","label":"Author","values":["Ambily, Anju"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012"]},{"key":"dc:date.issued","label":"Date","values":["2012"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Vascular Biology & Inflammation"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["King's College London"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://kclpure.kcl.ac.uk/portal/en/studentTheses/0754e26d-374a-485e-9387-41e074926048"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/0754e26d-374a-485e-9387-41e074926048","https://kclpure.kcl.ac.uk/portal/en/studentTheses/0754e26d-374a-485e-9387-41e074926048"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Platelet activation is essential in haemostasis and thrombosis and central to this role is cytosolic calcium (Ca2+) elevation. The two ways in which this can occur are release from intracellular Ca2+ stores and the entry of Ca2+ across the plasma membrane (PM). Changes in cytosolic Ca2+ are required to enable a variety of platelet responses. In platelets and other non-excitable cells, the major route of Ca2+ entry occurs as a result of Ca2+ depletion from intracellular stores, and is known as store operated Ca2+ entry (SOCE). STIM1 is the Ca2+ sensing protein of the endoplasmic reticulum (ER) which activates Orai channels in the plasma membrane allowing Ca + entry. However, not all of the details of Ca2+ entry are understood. In platelets, two other pathways also enable Ca2+ entry. The P2X1 receptor is a ligand gated ion channel activated by the binding of ATP. Second messengers (such as 1,2-diacyl-sn- glycerol [DAG]) and phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) may directly gate plasma membrane cation channels such as the transient receptor potential canonical 6 (TRPC6) channel. -- The main aim of this study was to examine the role of STIM1 and TRPC proteins in Ca2+ entry in human platelets. The TRPC1 protein was originally proposed to be a major component of the SOC channel based on the observation that a commercial preparation of an anti-TRPCl antibody against the channel impaired SOCE in platelets. However, in the current study I demonstrate the failure of this reagent to bind to TRPC1. The previously reported inhibitory effect on SOCE may be due in part to be a result of the azide component of the antibody preparation."]},{"key":"dc:title","label":"Title","values":["Studies of calcium signalling mechanisms in human platelets"]}]}],"canonical_facts":{"dc:contributor.advisor":["Authi, Kalwant Singh","Pearson, Jeremy David"],"dc:creator":["Ambily, Anju"],"dc:date":["2012"],"dc:date.issued":["2012"],"dc:description.abstract":["Platelet activation is essential in haemostasis and thrombosis and central to this role is cytosolic calcium (Ca2+) elevation. The two ways in which this can occur are release from intracellular Ca2+ stores and the entry of Ca2+ across the plasma membrane (PM). Changes in cytosolic Ca2+ are required to enable a variety of platelet responses. In platelets and other non-excitable cells, the major route of Ca2+ entry occurs as a result of Ca2+ depletion from intracellular stores, and is known as store operated Ca2+ entry (SOCE). 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