TY - JOUR

T1 - Atrium-specific ion channels in the zebrafish

T2 - A role of Iin atrial repolarization

AU - Skarsfeldt, M A

AU - Bomholtz, S H

AU - Lundegaard, P R

AU - Lopez-Izquierdo, A

AU - Tristani-Firouzi, M

AU - Bentzen, B H

N1 - © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

PY - 2018/7

Y1 - 2018/7

N2 - AIM: The zebrafish has emerged as a novel model for investigating cardiac physiology and pathology. The aim of this study was to investigate the atrium-specific ion channels responsible for shaping the atrial cardiac action potential in zebrafish.METHODS: Using quantitative polymerase chain reaction, we assessed the expression level of atrium-specific potassium channels. The functional role of these channels was studied by patch clamp experiments on isolated atrial and ventricular cardiomyocytes and by optical mapping of explanted adult zebrafish hearts. Finally, surface ECGs were recorded to establish possible in vivo roles of atrial ion channels.RESULTS: In isolated adult zebrafish hearts, we identified the expression of kcnk3, kcnk9, kcnn1, kcnn2, kcnn3, kcnj3 and kcnj5, the genes that encode the atrium-specific K2P, KCa2.x and Kir3.1/4 (KACh) ion channels. The electrophysiological data indicate that the acetylcholine-activated inward-rectifying current, IKACh,plays a major role in the zebrafish atrium, whereas K2P3.1/9.1 and KCa2.x channels do not appear to be involved in regulating the action potential in the zebrafish heart.CONCLUSION: We demonstrate that the acetylcholine-activated inward-rectifying current (IKACh) current plays a major role in the zebrafish atrium and that the zebrafish could potentially be a cost-effective and reliable model for pharmacological testing of atrium-specific IKAChmodulating compounds.

AB - AIM: The zebrafish has emerged as a novel model for investigating cardiac physiology and pathology. The aim of this study was to investigate the atrium-specific ion channels responsible for shaping the atrial cardiac action potential in zebrafish.METHODS: Using quantitative polymerase chain reaction, we assessed the expression level of atrium-specific potassium channels. The functional role of these channels was studied by patch clamp experiments on isolated atrial and ventricular cardiomyocytes and by optical mapping of explanted adult zebrafish hearts. Finally, surface ECGs were recorded to establish possible in vivo roles of atrial ion channels.RESULTS: In isolated adult zebrafish hearts, we identified the expression of kcnk3, kcnk9, kcnn1, kcnn2, kcnn3, kcnj3 and kcnj5, the genes that encode the atrium-specific K2P, KCa2.x and Kir3.1/4 (KACh) ion channels. The electrophysiological data indicate that the acetylcholine-activated inward-rectifying current, IKACh,plays a major role in the zebrafish atrium, whereas K2P3.1/9.1 and KCa2.x channels do not appear to be involved in regulating the action potential in the zebrafish heart.CONCLUSION: We demonstrate that the acetylcholine-activated inward-rectifying current (IKACh) current plays a major role in the zebrafish atrium and that the zebrafish could potentially be a cost-effective and reliable model for pharmacological testing of atrium-specific IKAChmodulating compounds.

U2 - 10.1111/apha.13049

DO - 10.1111/apha.13049

M3 - Journal article

C2 - 29412518

VL - 223

JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

IS - 3

M1 - e13049

ER -