Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange.

Stéphanie C Choisy,Hongwei Cheng,Jules C Hancox,Clive H Orchard,Andrew F James

doi:10.14814/phy2.12633

Stéphanie C Choisy, Hongwei Cheng + Show 3 more

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https://doi.org/10.14814/phy2.12633

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Journal: Physiological Reports	Publication Date: Nov 1, 2015
Citations: 34	License type: cc-by

Affiliation: University of Bristol

Abstract

The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35–37°C. Hyperpolarizing voltage commands from −40 mV elicited a Ba2+-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from −40 mV L-type Ca2+ current, ICa,L, was elicited with a half maximal activation voltage (V0.5) of −7.6 ± 1.2 mV (n = 24). ICa,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IKr) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to −40 mV, with an activation V0.5 of −10.7 ± 4.7 mV (n = 8). The IKr magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (−40 mV). Spontaneous APs (5.2 ± 0.5 sec−1; n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca2+ release by 1 μmol/L ryanodine, implicating intracellular Ca2+ cycling in murine AVN cell electrogenesis.

Highlights

The atrioventricular node (AVN) is an important component of the conduction system in mammalian hearts, with slow AVN conduction playing a key role in the normal sequence of atrial-ventricular excitation and contraction (Tawara 1906; Childers 1977; Meijler and Janse 1988)
Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society
There was no difference in mean cell surface area between Type 1 and Type 2 (If possessing) AVN cells in this study, though the mean cell capacitance of If-possessing cells in our study (34 pF) is higher than that reported by Marger and colleagues (20 pF) (Marger et al 2011b)

Summary

Introduction

The atrioventricular node (AVN) is an important component of the conduction system in mammalian hearts, with slow AVN conduction playing a key role in the normal sequence of atrial-ventricular excitation and contraction (Tawara 1906; Childers 1977; Meijler and Janse 1988). The AVN is normally the only route for excitation to pass from atria to ventricles and the slow conduction properties of the AVN can protect the ventricles from high atrial rates sustained during supraventricular tachycardias (SVTs) (Childers 1977; Selzer 1982; Meijler and Janse 1988). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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