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Article: Comparative mechanisms of 4-aminopyridine-resistant I(to) in human and rabbit atrial myocytes

TitleComparative mechanisms of 4-aminopyridine-resistant I(to) in human and rabbit atrial myocytes
Authors
Issue Date1995
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal Of Physiology - Heart And Circulatory Physiology, 1995, v. 269 n. 2 38-2, p. H463-H472 How to Cite?
AbstractThe cardiac transient outward current (I(to)) has been shown in several species to consist of two components: 1) a 4-aminopyridine (4-AP)-sensitive component (I(to1)) and 2) a 4-AP-resistant component (I(to2)). In rabbits, I(to2) is a Ca2+dependent Cl- current [I(Cl(Ca))]; similar mechanisms have been suggested to underlie I(to2) in human atrium. We used whole cell patch- clamp techniques to define the mechanism of I(to2) (defined as the component resistant to 5 mM 4-AP) in human atrial myocytes, with parallel experiments performed in rabbit atrial cells. In rabbit atrium, I(to2) activated more slowly than I(to1) and had a bell-shaped current-voltage (I-V) relation. Ryanodine suppressed a component of I(to) with properties similar to I(to2) in the rabbit, and a similar component recorded with pipette K+ replaced by Cs+ was suppressed by the substitution of methanesulfonate for Cl- in the superfusate. In human cells, a 4-AP-resistant I(to2) was recorded at a depolarizing pulse frequency of 1 Hz, but not at 0.1 Hz. I(to2) activated rapidly and inactivated earlier than I(to1), whereas its I-V relation was linear like that of I(to1). Ryanodine had no effect on human atrial I(to). When K+-free pipette solutions were used, no I(to) was recorded in 30 human atrial myocytes, and external Cl- replacement with methanesulfonate failed to reveal an I(to). In 13 human myocytes, isoproterenol increased I(Ca) but failed to activate an I(to) compatible with I(Cl(Ca)). Whereas caffeine suppressed human atrial I(to), it also suppressed I(to1) [in the presence of 200 μM Cd2+ to block I(Ca) and 5 mM intracellular ethylene glycol-bis(β- aminoethyl ether)-N,N,N',N'-tetraacetic acid to buffer intracellular Ca2+] in both human and rabbit atrium, indicating an action unrelated to Ca2+- triggered Ca2+ release. In conclusion, we were unable to demonstrate the presence of I(Cl(Ca)) in human atrial myocytes, and the 4-AP-resistant component of I(to) appeared to be due to 4-AP unblocking.
Persistent Identifierhttp://hdl.handle.net/10722/162094
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, GRen_US
dc.contributor.authorFeng, Jen_US
dc.contributor.authorWang, Zen_US
dc.contributor.authorFermini, Ben_US
dc.contributor.authorNattel, Sen_US
dc.date.accessioned2012-09-05T05:17:18Z-
dc.date.available2012-09-05T05:17:18Z-
dc.date.issued1995en_US
dc.identifier.citationAmerican Journal Of Physiology - Heart And Circulatory Physiology, 1995, v. 269 n. 2 38-2, p. H463-H472en_US
dc.identifier.issn0363-6135en_US
dc.identifier.urihttp://hdl.handle.net/10722/162094-
dc.description.abstractThe cardiac transient outward current (I(to)) has been shown in several species to consist of two components: 1) a 4-aminopyridine (4-AP)-sensitive component (I(to1)) and 2) a 4-AP-resistant component (I(to2)). In rabbits, I(to2) is a Ca2+dependent Cl- current [I(Cl(Ca))]; similar mechanisms have been suggested to underlie I(to2) in human atrium. We used whole cell patch- clamp techniques to define the mechanism of I(to2) (defined as the component resistant to 5 mM 4-AP) in human atrial myocytes, with parallel experiments performed in rabbit atrial cells. In rabbit atrium, I(to2) activated more slowly than I(to1) and had a bell-shaped current-voltage (I-V) relation. Ryanodine suppressed a component of I(to) with properties similar to I(to2) in the rabbit, and a similar component recorded with pipette K+ replaced by Cs+ was suppressed by the substitution of methanesulfonate for Cl- in the superfusate. In human cells, a 4-AP-resistant I(to2) was recorded at a depolarizing pulse frequency of 1 Hz, but not at 0.1 Hz. I(to2) activated rapidly and inactivated earlier than I(to1), whereas its I-V relation was linear like that of I(to1). Ryanodine had no effect on human atrial I(to). When K+-free pipette solutions were used, no I(to) was recorded in 30 human atrial myocytes, and external Cl- replacement with methanesulfonate failed to reveal an I(to). In 13 human myocytes, isoproterenol increased I(Ca) but failed to activate an I(to) compatible with I(Cl(Ca)). Whereas caffeine suppressed human atrial I(to), it also suppressed I(to1) [in the presence of 200 μM Cd2+ to block I(Ca) and 5 mM intracellular ethylene glycol-bis(β- aminoethyl ether)-N,N,N',N'-tetraacetic acid to buffer intracellular Ca2+] in both human and rabbit atrium, indicating an action unrelated to Ca2+- triggered Ca2+ release. In conclusion, we were unable to demonstrate the presence of I(Cl(Ca)) in human atrial myocytes, and the 4-AP-resistant component of I(to) appeared to be due to 4-AP unblocking.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Heart and Circulatory Physiologyen_US
dc.subject.mesh4-Aminopyridine - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAtrial Function - Drug Effectsen_US
dc.subject.meshCaffeine - Pharmacologyen_US
dc.subject.meshCalcium - Physiologyen_US
dc.subject.meshChlorides - Physiologyen_US
dc.subject.meshDrug Resistanceen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshMyocardium - Cytologyen_US
dc.subject.meshPatch-Clamp Techniquesen_US
dc.subject.meshPotassium Channels - Physiologyen_US
dc.subject.meshRabbitsen_US
dc.titleComparative mechanisms of 4-aminopyridine-resistant I(to) in human and rabbit atrial myocytesen_US
dc.typeArticleen_US
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_US
dc.identifier.authorityLi, GR=rp00476en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7653610-
dc.identifier.scopuseid_2-s2.0-0029095019en_US
dc.identifier.volume269en_US
dc.identifier.issue2 38-2en_US
dc.identifier.spageH463en_US
dc.identifier.epageH472en_US
dc.identifier.isiWOS:A1995RP46700008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLi, GR=7408462932en_US
dc.identifier.scopusauthoridFeng, J=7403884361en_US
dc.identifier.scopusauthoridWang, Z=7410039597en_US
dc.identifier.scopusauthoridFermini, B=6603996429en_US
dc.identifier.scopusauthoridNattel, S=36048738800en_US

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