{"id":{"repo_id":"radboud","oai_identifier":"oai:repository.ubn.ru.nl:2066/19366"},"canonical_url":"https://search.dev.ndltd.org/etd/radboud/oai:repository.ubn.ru.nl:2066/19366","repository":{"repo_id":"radboud","name":"Radboud University Nijmegen","base_url":"https://repository.ubn.ru.nl/oai/request"},"display":{"title":"Excitable fibroblasts! : ion channels, gap junctions, action potentials and calcium oscillations in normal rat kidney fibroblasts","abstract":"Contains fulltext : 19366.pdf (Publisher’s version ) (Open Access)","abstract_html":"Contains fulltext : 19366.pdf (Publisher’s version ) (Open Access)","abstract_has_math":false,"creators":["Harks, Erik Godefridus Antonius"],"institution":"[S.l. : s.n.]","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2003,"date_issued":"2003","date_published":"2003","updated_at":"2026-07-24T04:01:06Z","subjects":[],"languages":[],"rights":["(c) Erik Godefridus Antonius Harks, 2003"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9090174060"],"render_values":[{"text":"9090174060","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2066/19366","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Harks, Erik Godefridus Antonius"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2003"]},{"key":"dc:publisher","label":"Institution","values":["[S.l. : s.n.]"]},{"key":"dc:type","label":"Dc Type","values":["Doctoral thesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["(c) Erik Godefridus Antonius Harks, 2003"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://repository.ubn.ru.nl//bitstream/handle/2066/19366/19366.pdf","http://hdl.handle.net/2066/19366","9090174060"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Contains fulltext : 19366.pdf (Publisher’s version ) (Open Access)","During development and also in the adult organism cellular growth is strictly regulated by various control mechanisms that ensure cells to start and stop dividing at the proper time and place. Dysfunction of these intricate regulatory mechanisms may result in uncontrolled proliferation of cells and can be the basis for a large diversity of pathogenic conditions including cancer. In our studies we have used normal rat kidney (NRK) fibroblasts as a cellular model system for studying the mechanisms of density-dependent growth inhibition and alterations upon phenotypic transformation, and focused on the biophysical aspects of NRK cells including membrane potential, intracellular calcium dynamics and GJIC, in relation to their growth regulation. Since fibroblasts are considered as classical examples of non-excitable cells, it was rather surprising that NRK fibroblasts repetitively fired calcium action potentials when they were cultured to density-arrest. We have elucidated the excitability mechanism of NRK cells and demonstrated how an L-type calcium conductance, a calcium-activated chloride conductance, an inwardly rectifying potassium conductance, and gap junctional intercellular communication contribute to action potential firing and propagation. Moreover, we have shown that the cytosolic calcium concentration can oscillate in these cells by an intricate interplay between internal calcium stores and plasma membrane ion channels, thereby providing NRK cells with a timing mechanism. During our studies we discovered a novel property of fenamates and 2-aminoethoxydiphenyl borate (2-APB), namely their ability to block gap junctions. The uncoupling action of 2-APB is unique, since 2-APB appears to be the first gap junction blocker that does not affect plasma membrane channels. Thus, it can be used to study ion channel properties in single cells in undissociated tissues. Finally, we have shown that NRK cells become depolarized and secrete a biologically active prostaglandin (PGF2{alpha}) upon phenotypic transformation, which are both typical consequences of tumorigenic transformation.","168 p."]},{"key":"dc:title","label":"Title","values":["Excitable fibroblasts! : ion channels, gap junctions, action potentials and calcium oscillations in normal rat kidney fibroblasts"]}]}],"canonical_facts":{"dc:creator":["Harks, Erik Godefridus Antonius"],"dc:date":["2003"],"dc:description":["Contains fulltext : 19366.pdf (Publisher’s version ) (Open Access)","During development and also in the adult organism cellular growth is strictly regulated by various control mechanisms that ensure cells to start and stop dividing at the proper time and place. Dysfunction of these intricate regulatory mechanisms may result in uncontrolled proliferation of cells and can be the basis for a large diversity of pathogenic conditions including cancer. In our studies we have used normal rat kidney (NRK) fibroblasts as a cellular model system for studying the mechanisms of density-dependent growth inhibition and alterations upon phenotypic transformation, and focused on the biophysical aspects of NRK cells including membrane potential, intracellular calcium dynamics and GJIC, in relation to their growth regulation. Since fibroblasts are considered as classical examples of non-excitable cells, it was rather surprising that NRK fibroblasts repetitively fired calcium action potentials when they were cultured to density-arrest. We have elucidated the excitability mechanism of NRK cells and demonstrated how an L-type calcium conductance, a calcium-activated chloride conductance, an inwardly rectifying potassium conductance, and gap junctional intercellular communication contribute to action potential firing and propagation. Moreover, we have shown that the cytosolic calcium concentration can oscillate in these cells by an intricate interplay between internal calcium stores and plasma membrane ion channels, thereby providing NRK cells with a timing mechanism. During our studies we discovered a novel property of fenamates and 2-aminoethoxydiphenyl borate (2-APB), namely their ability to block gap junctions. The uncoupling action of 2-APB is unique, since 2-APB appears to be the first gap junction blocker that does not affect plasma membrane channels. Thus, it can be used to study ion channel properties in single cells in undissociated tissues. Finally, we have shown that NRK cells become depolarized and secrete a biologically active prostaglandin (PGF2{alpha}) upon phenotypic transformation, which are both typical consequences of tumorigenic transformation.","168 p."],"dc:identifier":["https://repository.ubn.ru.nl//bitstream/handle/2066/19366/19366.pdf","http://hdl.handle.net/2066/19366","9090174060"],"dc:publisher":["[S.l. : s.n.]"],"dc:rights":["(c) Erik Godefridus Antonius Harks, 2003"],"dc:title":["Excitable fibroblasts! : ion channels, gap junctions, action potentials and calcium oscillations in normal rat kidney fibroblasts"],"dc:type":["Doctoral thesis"]},"updated_at":"2026-07-24T04:01:06Z"}