{"id":{"repo_id":"heid-diss","oai_identifier":"oai:archiv.ub.uni-heidelberg.de:4312"},"canonical_url":"https://search.dev.ndltd.org/etd/heid-diss/oai:archiv.ub.uni-heidelberg.de:4312","repository":{"repo_id":"heid-diss","name":"Universität Heidelberg","base_url":"http://archiv.ub.uni-heidelberg.de/volltextserver/cgi/oai2"},"display":{"title":"Intravenous anaesthetics inhibit nicotinic receptor-induced membrane currents and Ca 2+ -transients in rat intracardiac neurons","abstract":"The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-mediated transients in intracellular free Ca2+ concentration ([Ca2+]i) and currents were investigated in neonatal rat intracardiac neurons using fura-2 photometry and patch-clamp recordings. Extensive preliminary tests using fura-2 containing solutions in the presence or absence of the anaesthetics were carried out to detect any interference of these drugs with the fura-2 fluorescence signal: Using photospectrometry and a ratiometric photometry set-up to carry out a series of calibrations of the fura-2 signal revealed that ratiometric fura-2 recordings can faithfully be carried out in the presence of clinically relevant concentrations (clinical EC50) of the i.v. anaesthetics studied. In fura-2 loaded neurons, nAChR activation evoked a transient increase in [Ca2+]i, which was reversibly inhibited by the clinical EC50 of the i.v. anaesthetic thiopental. The EC50 for thiopental inhibition of nAChR induced [Ca2+]i transients was 28 µM, close to the estimated clinical EC50 of thiopental (25 µM). However, control experiments using Ca2+ -channel blockers showed that voltage-gated Ca2+ -channels (Cav) are activated by the depolarization following nAChR activation and thus indirectly contribute to increases in [Ca2+]i. When fura-2 loaded neurons were voltage-clamped at -60 mV to eliminate any contribution of voltage-gated Ca2+ channels, then thiopental simultaneously inhibited nAChR-induced increases in [Ca2+]i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialyzed whole cell recordings by ~ 40 % at -120, -80 and -40 mV holding potential suggesting that the inhibition is voltage independent. Thiopental did not inhibit caffeine-induced [Ca2+]i transients, indicating that an inhibition of Ca2+ release from internal stores via ryanodine receptor (RyR) channels is unlikely. The barbiturate pentobarbital and the dissociative anaesthetic ketamine used at clinical EC50 concentrations were also shown to inhibit nAChR-induced increases in [Ca2+]i. In conclusion, thiopental and other i.v. anaesthetics may inhibit nAChR-induced currents and [Ca2+]i transients in intracardiac neurons by binding to nAChR and thereby may contribute to changes in heart rate and cardiac output under clinical conditions.","abstract_html":"The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-mediated transients in intracellular free Ca2+ concentration ([Ca2+]i) and currents were investigated in neonatal rat intracardiac neurons using fura-2 photometry and patch-clamp recordings. Extensive preliminary tests using fura-2 containing solutions in the presence or absence of the anaesthetics were carried out to detect any interference of these drugs with the fura-2 fluorescence signal: Using photospectrometry and a ratiometric photometry set-up to carry out a series of calibrations of the fura-2 signal revealed that ratiometric fura-2 recordings can faithfully be carried out in the presence of clinically relevant concentrations (clinical EC50) of the i.v. anaesthetics studied. In fura-2 loaded neurons, nAChR activation evoked a transient increase in [Ca2+]i, which was reversibly inhibited by the clinical EC50 of the i.v. anaesthetic thiopental. The EC50 for thiopental inhibition of nAChR induced [Ca2+]i transients was 28 µM, close to the estimated clinical EC50 of thiopental (25 µM). However, control experiments using Ca2+ -channel blockers showed that voltage-gated Ca2+ -channels (Cav) are activated by the depolarization following nAChR activation and thus indirectly contribute to increases in [Ca2+]i. When fura-2 loaded neurons were voltage-clamped at -60 mV to eliminate any contribution of voltage-gated Ca2+ channels, then thiopental simultaneously inhibited nAChR-induced increases in [Ca2+]i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialyzed whole cell recordings by ~ 40 % at -120, -80 and -40 mV holding potential suggesting that the inhibition is voltage independent. Thiopental did not inhibit caffeine-induced [Ca2+]i transients, indicating that an inhibition of Ca2+ release from internal stores via ryanodine receptor (RyR) channels is unlikely. The barbiturate pentobarbital and the dissociative anaesthetic ketamine used at clinical EC50 concentrations were also shown to inhibit nAChR-induced increases in [Ca2+]i. In conclusion, thiopental and other i.v. anaesthetics may inhibit nAChR-induced currents and [Ca2+]i transients in intracardiac neurons by binding to nAChR and thereby may contribute to changes in heart rate and cardiac output under clinical conditions.","abstract_has_math":false,"creators":["Weber, Martin"],"institution":"Universität Heidelberg","degree_name":null,"degree_level":"thesis.doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Dr. Rainer H.A. Fink"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2003,"date_issued":"2003-12-08","date_published":"2003-12-08","updated_at":"2026-07-24T02:29:42Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://www.ub.uni-heidelberg.de/archiv/4312","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr. Rainer H.A. Fink"]},{"key":"dc:creator","label":"Author","values":["Weber, Martin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Universitätsbibliothek Heidelberg"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["thesis.doctoral"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Universität Heidelberg"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-mediated transients in intracellular free Ca2+ concentration ([Ca2+]i) and currents were investigated in neonatal rat intracardiac neurons using fura-2 photometry and patch-clamp recordings. Extensive preliminary tests using fura-2 containing solutions in the presence or absence of the anaesthetics were carried out to detect any interference of these drugs with the fura-2 fluorescence signal: Using photospectrometry and a ratiometric photometry set-up to carry out a series of calibrations of the fura-2 signal revealed that ratiometric fura-2 recordings can faithfully be carried out in the presence of clinically relevant concentrations (clinical EC50) of the i.v. anaesthetics studied. In fura-2 loaded neurons, nAChR activation evoked a transient increase in [Ca2+]i, which was reversibly inhibited by the clinical EC50 of the i.v. anaesthetic thiopental. The EC50 for thiopental inhibition of nAChR induced [Ca2+]i transients was 28 µM, close to the estimated clinical EC50 of thiopental (25 µM). However, control experiments using Ca2+ -channel blockers showed that voltage-gated Ca2+ -channels (Cav) are activated by the depolarization following nAChR activation and thus indirectly contribute to increases in [Ca2+]i. When fura-2 loaded neurons were voltage-clamped at -60 mV to eliminate any contribution of voltage-gated Ca2+ channels, then thiopental simultaneously inhibited nAChR-induced increases in [Ca2+]i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialyzed whole cell recordings by ~ 40 % at -120, -80 and -40 mV holding potential suggesting that the inhibition is voltage independent. Thiopental did not inhibit caffeine-induced [Ca2+]i transients, indicating that an inhibition of Ca2+ release from internal stores via ryanodine receptor (RyR) channels is unlikely. The barbiturate pentobarbital and the dissociative anaesthetic ketamine used at clinical EC50 concentrations were also shown to inhibit nAChR-induced increases in [Ca2+]i. In conclusion, thiopental and other i.v. anaesthetics may inhibit nAChR-induced currents and [Ca2+]i transients in intracardiac neurons by binding to nAChR and thereby may contribute to changes in heart rate and cardiac output under clinical conditions."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Intravenous anaesthetics inhibit nicotinic receptor-induced membrane currents and Ca 2+ -transients in rat intracardiac neurons","Intravenöse Anästhetika hemmen nikotinerg induzierte Membranströme und Ca 2+ -Transienten in Herzganglienneuronen der Ratte"]}]}],"canonical_facts":{"dc:contributor":["Dr. Rainer H.A. Fink"],"dc:creator":["Weber, Martin"],"dc:description.abstract":["The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-mediated transients in intracellular free Ca2+ concentration ([Ca2+]i) and currents were investigated in neonatal rat intracardiac neurons using fura-2 photometry and patch-clamp recordings. Extensive preliminary tests using fura-2 containing solutions in the presence or absence of the anaesthetics were carried out to detect any interference of these drugs with the fura-2 fluorescence signal: Using photospectrometry and a ratiometric photometry set-up to carry out a series of calibrations of the fura-2 signal revealed that ratiometric fura-2 recordings can faithfully be carried out in the presence of clinically relevant concentrations (clinical EC50) of the i.v. anaesthetics studied. In fura-2 loaded neurons, nAChR activation evoked a transient increase in [Ca2+]i, which was reversibly inhibited by the clinical EC50 of the i.v. anaesthetic thiopental. The EC50 for thiopental inhibition of nAChR induced [Ca2+]i transients was 28 µM, close to the estimated clinical EC50 of thiopental (25 µM). However, control experiments using Ca2+ -channel blockers showed that voltage-gated Ca2+ -channels (Cav) are activated by the depolarization following nAChR activation and thus indirectly contribute to increases in [Ca2+]i. When fura-2 loaded neurons were voltage-clamped at -60 mV to eliminate any contribution of voltage-gated Ca2+ channels, then thiopental simultaneously inhibited nAChR-induced increases in [Ca2+]i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialyzed whole cell recordings by ~ 40 % at -120, -80 and -40 mV holding potential suggesting that the inhibition is voltage independent. Thiopental did not inhibit caffeine-induced [Ca2+]i transients, indicating that an inhibition of Ca2+ release from internal stores via ryanodine receptor (RyR) channels is unlikely. The barbiturate pentobarbital and the dissociative anaesthetic ketamine used at clinical EC50 concentrations were also shown to inhibit nAChR-induced increases in [Ca2+]i. In conclusion, thiopental and other i.v. anaesthetics may inhibit nAChR-induced currents and [Ca2+]i transients in intracardiac neurons by binding to nAChR and thereby may contribute to changes in heart rate and cardiac output under clinical conditions."],"dc:format.medium":["application/pdf"],"dc:publisher":["Universitätsbibliothek Heidelberg"],"dc:title":["Intravenous anaesthetics inhibit nicotinic receptor-induced membrane currents and Ca 2+ -transients in rat intracardiac neurons","Intravenöse Anästhetika hemmen nikotinerg induzierte Membranströme und Ca 2+ -Transienten in Herzganglienneuronen der Ratte"],"dc:type":["doctoralThesis"],"thesis:degree_level":["thesis.doctoral"],"thesis:institution_name":["Universität Heidelberg"]},"updated_at":"2026-07-24T02:29:42Z"}