The versatility of Ca2+ as a messenger regulating a myriad of signalling events requires that the concentration of Ca2+ ions in the cytoplasm be highly regulated. Capacitative Ca2+ entry (CCE) or store-operated Ca2+ (SOC) entry, whereby the depletion of intracellular Ca2+ stores induces the influx of Ca2+ across the plasma membrane, plays a crucial role in Ca2+ signalling. Despite the recent advances in elucidating the entry pathway, its molecular identity, biophysical properties and store-depletion signal remains undefined. Thapsigargin (TG), a sarcoplasmic/endoplasmic reticulum Ca2+ A TPase pump (SERCA), inhibitor induces passive depletion of the internal Ca2+ stores and triggers CCE. The universality of this signal has been widely accepted and TG has proven to be a valuable tool in studying CCE. The neuronal cell line NG 115 -401 L lacks the TG activated Ca2+ influx pathway. Agonists of the ryanodine receptor (RyR); chlorom- cresol (CMC), polychlorinated biphenyl 95 (PCB), ryanodine, caffeine, and that of the inositol-1 ,4 ,5-trisphosphate receptor (IP3R), bradykinin, effectively couple to the activation of Ca2+ influx in these cells. The Ca2+ influx signal due to these agonists can be inhibited by SOC blockers such as La3+, Zn2+, Ni2+ and SF&F 96365. Thapsigargin, CMC and PCB95 share the same Ca2+ releasable pools in the 401 L cells. Our data thus suggests that the channels present in the 401 L cells are likely to be receptor-activated channels rather than the store-depletion activated channels. Cell viability studies show that thapsigargin (25 nM) can decrease viability by 75% within 24 hrs and the RyR agonist caffeine decreased viability to <60% within 24hrs. CMC, PCB95 and ryanodine also were cytotoxic at higher doses. Nuclear fragmentation patterns and activation of caspase-3 in thapsigargin and caffeine-treated cells suggest the induction of apoptosis within 12 hrs of treatment. The treated cells were shown to generate nitric oxide, a potential apoptosis inducing agent.
","abstract_html":"<p>The versatility of Ca<sup>2+</sup> as a messenger regulating a myriad of signalling events requires that the concentration of Ca<sup>2+</sup> ions in the cytoplasm be highly regulated. Capacitative Ca<sup>2+</sup> entry (CCE) or store-operated Ca<sup>2+</sup> (SOC) entry, whereby the depletion of intracellular Ca<sup>2+</sup> stores induces the influx of Ca<sup>2+</sup> across the plasma membrane, plays a crucial role in Ca<sup>2+</sup> signalling. Despite the recent advances in elucidating the entry pathway, its molecular identity, biophysical properties and store-depletion signal remains undefined. Thapsigargin (TG), a sarcoplasmic/endoplasmic reticulum Ca<sup>2+</sup> A TPase pump (SERCA), inhibitor induces passive depletion of the internal Ca<sup>2+</sup> stores and triggers CCE. The universality of this signal has been widely accepted and TG has proven to be a valuable tool in studying CCE. The neuronal cell line NG 115 -401 L lacks the TG activated Ca<sup>2+</sup> influx pathway. Agonists of the ryanodine receptor (RyR); chlorom- cresol (CMC), polychlorinated biphenyl 95 (PCB), ryanodine, caffeine, and that of the inositol-1 ,4 ,5-trisphosphate receptor (IP<sub>3</sub>R), bradykinin, effectively couple to the activation of Ca<sup>2+</sup> influx in these cells. The Ca<sup>2+</sup> influx signal due to these agonists can be inhibited by SOC blockers such as La<sup>3+</sup>, Zn<sup>2+</sup>, Ni<sup>2+</sup> and SF&F 96365. Thapsigargin, CMC and PCB95 share the same Ca<sup>2+</sup> releasable pools in the 401 L cells. Our data thus suggests that the channels present in the 401 L cells are likely to be receptor-activated channels rather than the store-depletion activated channels. Cell viability studies show that thapsigargin (25 nM) can decrease viability by 75% within 24 hrs and the RyR agonist caffeine decreased viability to <60% within 24hrs. CMC, PCB95 and ryanodine also were cytotoxic at higher doses. Nuclear fragmentation patterns and activation of caspase-3 in thapsigargin and caffeine-treated cells suggest the induction of apoptosis within 12 hrs of treatment. The treated cells were shown to generate nitric oxide, a potential apoptosis inducing agent.</p>","abstract_has_math":false,"creators":["Bose, Diptiman Dipen"],"institution":null,"degree_name":"Master of Science (M.S.)","degree_level":"Thesis - Pacific Access Restricted","degree_discipline":"Pharmaceutical and Chemical Sciences","degree_department":null,"school":null,"contributors":["David Thomas"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2002,"date_issued":"2002-01-01T08:00:00Z","date_published":"2002-01-01T08:00:00Z","updated_at":"2026-07-24T05:36:28Z","subjects":["Cellular signal transduction","Neural transmission Regulation","Cells Growth Regulation","Ryanodine","Calcium in the body","Calcium Physiological effect","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":[],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://scholarlycommons.pacific.edu/uop_etds/566","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["David Thomas"]},{"key":"dc:creator","label":"Author","values":["Bose, Diptiman Dipen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-06-29T09:02:41Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmaceutical and Chemical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis - Pacific Access Restricted"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (M.S.)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cellular signal transduction","Neural transmission Regulation","Cells Growth Regulation","Ryanodine","Calcium in the body","Calcium Physiological effect","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarlycommons.pacific.edu/uop_etds/566"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The versatility of Ca2+ as a messenger regulating a myriad of signalling events requires that the concentration of Ca2+ ions in the cytoplasm be highly regulated. Capacitative Ca2+ entry (CCE) or store-operated Ca2+ (SOC) entry, whereby the depletion of intracellular Ca2+ stores induces the influx of Ca2+ across the plasma membrane, plays a crucial role in Ca2+ signalling. Despite the recent advances in elucidating the entry pathway, its molecular identity, biophysical properties and store-depletion signal remains undefined. Thapsigargin (TG), a sarcoplasmic/endoplasmic reticulum Ca2+ A TPase pump (SERCA), inhibitor induces passive depletion of the internal Ca2+ stores and triggers CCE. The universality of this signal has been widely accepted and TG has proven to be a valuable tool in studying CCE. The neuronal cell line NG 115 -401 L lacks the TG activated Ca2+ influx pathway. Agonists of the ryanodine receptor (RyR); chlorom- cresol (CMC), polychlorinated biphenyl 95 (PCB), ryanodine, caffeine, and that of the inositol-1 ,4 ,5-trisphosphate receptor (IP3R), bradykinin, effectively couple to the activation of Ca2+ influx in these cells. The Ca2+ influx signal due to these agonists can be inhibited by SOC blockers such as La3+, Zn2+, Ni2+ and SF&F 96365. Thapsigargin, CMC and PCB95 share the same Ca2+ releasable pools in the 401 L cells. Our data thus suggests that the channels present in the 401 L cells are likely to be receptor-activated channels rather than the store-depletion activated channels. Cell viability studies show that thapsigargin (25 nM) can decrease viability by 75% within 24 hrs and the RyR agonist caffeine decreased viability to <60% within 24hrs. CMC, PCB95 and ryanodine also were cytotoxic at higher doses. Nuclear fragmentation patterns and activation of caspase-3 in thapsigargin and caffeine-treated cells suggest the induction of apoptosis within 12 hrs of treatment. The treated cells were shown to generate nitric oxide, a potential apoptosis inducing agent.
"]},{"key":"dc:source","label":"Dc Source","values":["144"]},{"key":"dc:title","label":"Title","values":["Role of ryanodine receptors in neuronal calcium signalling and growth control"]}]}],"canonical_facts":{"dc:contributor":["David Thomas"],"dc:creator":["Bose, Diptiman Dipen"],"dc:date.available":["2018-06-29T09:02:41Z"],"dc:description.abstract":["The versatility of Ca2+ as a messenger regulating a myriad of signalling events requires that the concentration of Ca2+ ions in the cytoplasm be highly regulated. Capacitative Ca2+ entry (CCE) or store-operated Ca2+ (SOC) entry, whereby the depletion of intracellular Ca2+ stores induces the influx of Ca2+ across the plasma membrane, plays a crucial role in Ca2+ signalling. Despite the recent advances in elucidating the entry pathway, its molecular identity, biophysical properties and store-depletion signal remains undefined. Thapsigargin (TG), a sarcoplasmic/endoplasmic reticulum Ca2+ A TPase pump (SERCA), inhibitor induces passive depletion of the internal Ca2+ stores and triggers CCE. The universality of this signal has been widely accepted and TG has proven to be a valuable tool in studying CCE. The neuronal cell line NG 115 -401 L lacks the TG activated Ca2+ influx pathway. Agonists of the ryanodine receptor (RyR); chlorom- cresol (CMC), polychlorinated biphenyl 95 (PCB), ryanodine, caffeine, and that of the inositol-1 ,4 ,5-trisphosphate receptor (IP3R), bradykinin, effectively couple to the activation of Ca2+ influx in these cells. The Ca2+ influx signal due to these agonists can be inhibited by SOC blockers such as La3+, Zn2+, Ni2+ and SF&F 96365. Thapsigargin, CMC and PCB95 share the same Ca2+ releasable pools in the 401 L cells. Our data thus suggests that the channels present in the 401 L cells are likely to be receptor-activated channels rather than the store-depletion activated channels. Cell viability studies show that thapsigargin (25 nM) can decrease viability by 75% within 24 hrs and the RyR agonist caffeine decreased viability to <60% within 24hrs. CMC, PCB95 and ryanodine also were cytotoxic at higher doses. Nuclear fragmentation patterns and activation of caspase-3 in thapsigargin and caffeine-treated cells suggest the induction of apoptosis within 12 hrs of treatment. The treated cells were shown to generate nitric oxide, a potential apoptosis inducing agent.
"],"dc:identifier":["https://scholarlycommons.pacific.edu/uop_etds/566"],"dc:rights":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:source":["144"],"dc:subject":["Cellular signal transduction","Neural transmission Regulation","Cells Growth Regulation","Ryanodine","Calcium in the body","Calcium Physiological effect","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"],"dc:title":["Role of ryanodine receptors in neuronal calcium signalling and growth control"],"thesis:degree_discipline":["Pharmaceutical and Chemical Sciences"],"thesis:degree_level":["Thesis - Pacific Access Restricted"],"thesis:degree_name":["Master of Science (M.S.)"]},"updated_at":"2026-07-24T05:36:28Z"}