{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:29:38Z","timestamp":1762144178243,"version":"3.28.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypokalaemia is one of the important risk factors for development of torsades de pointes. We recently reported that hypokalaemia increased the electrocardiographic QT interval in rats treated with quinidine, but did not alter the arrhythmogenic potency of quinidine. In this study, we have investigated the influence of extracellular potassium concentration ([K+]o) on the inhibition of several types of cardiac potassium currents by quinidine. Such types of currents include the delayed rectifier potassium current (IK), the transient outward current (Ito), and the inward rectifier potassium current (IK1), as measured in isolated rat ventricular cells using patch-clamp techniques.<\/jats:p>\n               <jats:p>Concentration-dependent effects of quinidine on IK, Ito, and IK1 were evaluated under both normal ([K+]o = 5.4 mM) and hypokalaemic ([K+]o = 3.5 mM) conditions. In contrast to both IK and Ito, which were barely influenced by changes in [K+]o, IK1 was significantly inhibited by hypokalaemia. Furthermore, while quinidine suppressed both IK and Ito in a concentration-dependent manner, the inhibitory potency of quinidine on these currents was not influenced by changes in [K+]o. The respective normal and hypokalaemic IC50 values for quinidine were 11.4 and 10.0 \u03bcM (IK), and 17.6 and 17.3 \u03bcM (Ito). Although higher concentrations of quinidine were required to inhibit IK1, the inhibitory potency of quinidine was also found to be insensitive to changes in [K+]o. Thus, in rats, the inhibitory potency of quinidine for the K+ current-types IK, Ito and IK1 is barely influenced by changes in [K+]o.<\/jats:p>\n               <jats:p>These findings are consistent with our previous report showing that the QT-prolonging potency of quinidine was not altered under hypokalaemic conditions. However, whilst hypokalaemia does not affect IK or Ito, it can inhibit IK1 and can result in QT prolongation in-vivo.<\/jats:p>","DOI":"10.1211\/0022357001773571","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T23:43:52Z","timestamp":1058571832000},"page":"99-105","source":"Crossref","is-referenced-by-count":12,"title":["Influence of Extracellular K+ Concentrations on Quinidine-induced K+ Current Inhibition in Rat Ventricular Myocytes"],"prefix":"10.1093","volume":"52","author":[{"given":"Michiko","family":"Hirota","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-8655,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisakazu","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-8655,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Hanada","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-8655,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-8655,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Kotaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Research Hospital, The Institute of Medical Science, The University of Tokyo , Shirokanedai, Minato-ku, Tokyo 108-0071,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chiba University School of Medicine , Inohana, Chuo-ku, Chiba 260-8670,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruaki","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chiba University School of Medicine , Inohana, Chuo-ku, Chiba 260-8670,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuji","family":"Iga","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-8655,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,1,1]]},"reference":[{"key":"2024103110050489200_cit1","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1085\/jgp.97.5.973","article-title":"Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes","volume":"97","author":"Apkon","year":"1991","journal-title":"J. Gen. Physiol."},{"key":"2024103110050489200_cit2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S0006-3495(91)82207-X","article-title":"Single inward rectifier potassium channels in guinea pig ventricular myocytes: effects of quinidine","volume":"59","author":"Balser","year":"1991","journal-title":"Biophys. J."},{"key":"2024103110050489200_cit3","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/BF03015102","article-title":"Diuretic-induced hypokalaemia inducing torsades de pointes","volume":"42","author":"Chvilicek","year":"1995","journal-title":"Can. J. Anaesth."},{"key":"2024103110050489200_cit4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1161\/01.RES.50.1.17","article-title":"Mechanisms of action of lidocaine and quinidine on action potential duration in rabbit cardiac Purkinje fibres: an effect of steady-state sodium current","volume":"50","author":"Colatsky","year":"1982","journal-title":"Circ. 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