PhD Scientific Days 2020

Health Sciences Lectures

Comparison of Ion Channel Inhibitor Effects in Human and Rat Cardiac Ventricular Action Potentials Preparations

Előadó neve

Dr. Árpádffy-Lovas, Tamás

Előadó munkahelye

Department of Pharmachology and Pharmacotherapy, Faculty of Medicine, University of Szeged

Előadó telefonszáma

+36705681272

Előadó e-mail címe

arpadffy-lovas.tamas@med.u-szeged.hu

Az előadás címe

Comparison of Ion Channel Inhibitor Effects in Human and Rat Cardiac Ventricular Action Potentials Preparations

Szerző(k) neve és munkahelye

Tamás Árpádffy-Lovas1, Beáta Baláti1, Miklós Bitay2, Norbert László Jost1, Norbert Nagy1, István Baczkó1, László Virág1, András Varró1

1 Department of Pharmachology and Pharmacotherapy, Faculty of Medicine, University of Szeged

2 2nd Department of Internal Medicine and Cardiology Center, Albert Szent-Györgyi Clinical Center, University of Szeged, Department of Cardiac Surgery

Szekció

Health Sciences Lectures

Language of the presentation

English

Section, first choice

Health Sciences

Section, second choice

Pharmaceutical Sciences

Összefoglaló szövege

Introduction
Rodent models, such as rats and mice, are commonly used as model organisms in health sciences, due to their higher accessibility compared to larger animals (dog, pig, goat) and the availability of the toolset for their genetic manipulation. However, the translatability of data gathered from rodents is unclear in the field of electrophysiology.

Aims:
The aim of this study was to compare the effect of variuos channel blocking agents in human and rat cardiac preparations.

Method:
Ventricular preparations (papillary muscles and trablecules) were studied from human (n=58) and rat (n=36), using the conventional microelectrode technique at basic cycle length of 1000 ms. We assessed the effect of ion channel blockers HMR-1556 (500 nM; IKs), chromanol 293B (100 uM; IKs>Ito), dofetilide (50 nM; IKr); 4-aminopyridine (50-100 uM; IKur>>Ito), XEN-D101 (1-3 uM; IKur), and barium chloride (10 uM, IK1).

Results:
Action potential duration (APD90) of human ventricular preparations was 285‐± 6.7 ms (mean ± SEM), in rat it was 54 ± 3.5 ms. HMR-1556 caused no significant change in either of the preparation types. Subsequent administration of chromanol caused no change either in human preparations, but in rat it induced significant prolongation. Dofetilide significantly prolonged repolarization in human, but caused no changes in rat. In human preparations 4-aminopyridine induced a slight prolongation, but no such effect was detectable in rat. XEN-D101 did not affect human repolarization, but significantly prolonged that of rat preparations. Barium chloride significantly prolonged action potential duration both in human and rat preparations.

Conclusion:
Rodent action potential is characterized by rapid repolarization and no plateau phase, which is a distinctive difference compared to large animals. Our findings suggest that the cardiac ion channel composition of rodents also differs from that of human. Thus, utililization of rodents instead of large animals may not be advisable in cardiac electrophyisiological research.

Additional Information

Supervisor: András Varró
E-mail address: varro.andras@med.u-szeged.hu
Acknowledgments:
This work was funded by the National Research Development and Innovation Office (NKFIH K‑119992 and GINOP‑2.3.2.‑15-2016‑00047), the Ministry of Human Capacities Hungary (20391‑3/2018/FEKUSTRAT and EFOP‑3.6.2‑16‑2017‑00006), the UNKP‑19‑3‑SZTE‑5 (New National Excellence Program of the Ministry for Innovation and Technology)."

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4717

Start

10:20

End

10:35

Authors (legacy)

Tamás Árpádffy-Lovas1, Beáta Baláti1, Miklós Bitay2, Norbert László Jost1, Norbert Nagy1, István Baczkó1, László Virág1, András Varró1

1 Department of Pharmachology and Pharmacotherapy, Faculty of Medicine, University of Szeged

2 2nd Department of Internal Medicine and Cardiology Center, Albert Szent-Györgyi Clinical Center, University of Szeged, Department of Cardiac Surgery