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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

To understand the large inter-species variations in drug effects on repolarization, the properties of the rapid (IKr) and the slow (IKs) components of the delayed rectifier potassium currents were compared in myocytes isolated from undiseased human donor (HM), dog (DM), rabbit (RM) and guinea pig (GM) ventricles by applying the patch clamp and conventional microelectrode techniques at 37 °C. The amplitude of the E-4031-sensitive IKr tail current measured at −40 mV after a 1 s long test pulse of 20 mV, which was very similar in HM and DM but significant larger in RM and GM. The L-735,821-sensitive IKs tail current was considerably larger in GM than in RM. In HM, the IKs tail was even smaller than in DM. At 30 mV, the IKr component was activated extremely rapidly and monoexponentially in each studied species. The deactivation of the IKr component in HM, DM, and RM measured at −40 mV. After a 30 mV pulse, it was slow and biexponential, while in GM, the IKr tail current was best fitted triexponentially. At 30 mV, the IKs component activated slowly and had an apparent monoxponential time course in HM, DM, and RM. In contrast, in GM, the activation was clearly biexponential. In HM, DM, and RM, IKs component deactivation measured at −40 mV was fast and monoexponential, while in GM, in addition to the fast component, another slower component was also revealed. These results suggest that the IK in HM resembles that measured in DM and RM and considerably differs from that observed in GM. These findings suggest that the dog and rabbit are more appropriate species than the guinea pig for preclinical evaluation of new potential drugs expected to affect cardiac repolarization.

Details

Title
A Comparative Study of the Rapid (IKr) and Slow (IKs) Delayed Rectifier Potassium Currents in Undiseased Human, Dog, Rabbit, and Guinea Pig Cardiac Ventricular Preparations
Author
Ágoston, Márta 1 ; Kohajda, Zsófia 2 ; Virág, László 3 ; Baláti, Beáta 1 ; Nagy, Norbert 4 ; Lengyel, Csaba 5 ; Bitay, Miklós 6   VIAFID ORCID Logo  ; Bogáts, Gábor 6 ; Vereckei, András 7 ; Papp, Julius Gy 4 ; Varró, András 8 ; Jost, Norbert 8   VIAFID ORCID Logo 

 Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, P.O. Box 427, 6701 Szeged, Hungary 
 HUN-REN-SZTE Research Group for Cardiovascular Pharmacology, 6701 Szeged, Hungary 
 Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, P.O. Box 427, 6701 Szeged, Hungary; Interdisciplinary Research and Development and Innovation Centre of Excellence, University of Szeged, 6720 Szeged, Hungary 
 Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, P.O. Box 427, 6701 Szeged, Hungary; HUN-REN-SZTE Research Group for Cardiovascular Pharmacology, 6701 Szeged, Hungary 
 Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary 
 Department of Cardiac Surgery, Albert Szent-Györgyi Medical School, University of Szeged, 6742 Szeged, Hungary 
 Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary 
 Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, P.O. Box 427, 6701 Szeged, Hungary; HUN-REN-SZTE Research Group for Cardiovascular Pharmacology, 6701 Szeged, Hungary; Interdisciplinary Research and Development and Innovation Centre of Excellence, University of Szeged, 6720 Szeged, Hungary 
First page
1091
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
14248247
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3098042586
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.