Pacemaker activity and ionic currents in mouse atrioventricular node cells

Abstract

It is well established that Pacemaker activity of the sino-atrial node (SAN) initiates the heartbeat. However, the atrioventricular node (AVN) can generate viable pacemaker activity in case of SAN failure, but we have limited knowledge of the ionic bases of AVN automaticity. We characterized pacemaker activity and ionic currents in automatic myocytes of the mouse AVN. Pacemaking of AVN cells (AVNCs) was lower than that of SAN pacemaker cells (SANCs), both in control conditions and upon perfusion of isoproterenol (ISO). Block of I(Na) by tetrodotoxin (TTX) or of I(Ca,L) by isradipine abolished AVNCs pacemaker activity. TTX-resistant (I(Nar)) and TTX-sensitive (I(Nas)) Na(+) currents were recorded in mouse AVNCs, as well as T-(I(Ca,T)) and L-type (I(Ca,L)) Ca(2+) currents I(Ca,L) density was lower than in SANCs (51%). The density of the hyperpolarization-activated current, (I(f)) and that of the fast component of the delayed rectifier current (I(Kr)) were, respectively, lower (52%) and higher (53%) in AVNCs than in SANCs. Pharmacological inhibition of I(f) by 3 µM ZD-7228 reduced pacemaker activity by 16%, suggesting a relevant role for I(f) in AVNCs automaticity. Some AVNCs expressed also moderate densities of the transient outward K(+) current (I(to)). In contrast, no detectable slow component of the delayed rectifier current (I(Ks)) could be recorded in AVNCs. The lower densities of I(f) and I(Ca,L), as well as higher expression of I(Kr) in AVNCs than in SANCs may contribute to the intrinsically slower AVNCs pacemaking than that of SANCs.

Aromatase knockout mice reveal an impact of estrogen on drug-induced alternation of murine electrocardiography parameters

“…3 mERG expression in Fig. 1B is consistent with the functional I Kr expression in adult murine ventricular myocytes being rather low (Trépanier-Boulay et al, 2004), but I Kr expressions in the sinoatrial and atrioventricular (A-V) node are high enough to contribute to pacemaker activity of these cells (Marger et al, 2011), implying that I Kr blockade alters normal electrical function from sinoatrial to A-V node. Thus, to examine in vivo impacts of murine I Kr modulation, HR and A-V nodal conduction times (PR intervals) were intensively studied on surface ECG.…”

Ion channel-kinase TRPM 7 is required for maintaining cardiac automaticity

“…Cellular Electrophysiology. I Trpm7 , I f , I CaL , and I CaT were measured in the whole-cell configuration as previously described (7,40). Cellular automaticity was recorded under perforated-patch conditions using β-escin as previously described (40).…”

Functional Expression and Regulation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (HCN) in Mouse iPS Cell-derived Cardiomyocytes afterUTF1-Neo Selection

“…Most CMs recorded in the late stage of differentiation possess detectable I f currents and beat faster with regular rhythm. The presence of I f currents in most CMs at the late stage compared with the early stage of differentiation shows an ongoing maturation and the expression of HCN and others ion channels, which has been suggested to contribute to spontaneous activity in neonatal and adult CMs [4,45,46]. The leftward shift of half maximal activation potential of I f current may be explained by modifications in channel composition during the developmental process.…”