Burst pacemaker activity of the sinoatrial node in sodium-calcium exchanger knockout mice.

In sinoatrial node (SAN) cells, electrogenic sodium-calcium exchange (NCX) is the dominant calcium (Ca) efflux mechanism. However, the role of NCX in the generation of SAN automaticity is controversial. To investigate the contribution of NCX to pacemaking in the SAN, we performed optical voltage mapping and high-speed 2D laser scanning confocal microscopy (LSCM) of Ca dynamics in an ex vivo intact SAN/atrial tissue preparation from atrial-specific NCX knockout (KO) mice.

Complete atrial-specific knockout of sodium-calcium exchange eliminates sinoatrial node pacemaker activity.

The origin of sinoatrial node (SAN) pacemaker activity in the heart is controversial. The leading candidates are diastolic depolarization by "funny" current (If) through HCN4 channels (the "Membrane Clock" hypothesis), depolarization by cardiac Na-Ca exchange (NCX1) in response to intracellular Ca cycling (the "Calcium Clock" hypothesis), and a combination of the two ("Coupled Clock"). To address this controversy, we used Cre/loxP technology to generate atrial-specific NCX1 KO mice.

Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers.

Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Ca(i)) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing.

Effect of metabolic inhibition on couplon behavior in rabbit ventricular myocytes.

We investigated the effect of combined inhibition of oxidative and glycolytic metabolism on L-type Ca(2+) channels (LCCs) and Ca(2+) spikes in isolated patch-clamped rabbit ventricular myocytes. Metabolic inhibition (MI) reduced LCC open probability, increased null probability, increased first latency, and decreased open time but left conductance unchanged. These results explain the reduction in macroscopic Ca(2+) current observed during MI.

Short-term cardiac memory and mother rotor fibrillation.

Short-term cardiac memory refers to the effects of pacing history on action potential duration (APD). Although the ionic mechanisms for short-term memory occurring over many heartbeats (also called APD accommodation) are poorly understood, they may have important effects on reentry and fibrillation. To explore this issue, we incorporated a generic memory current into the Phase I Luo and Rudy action potential model, which lacks short-term memory.

Atrioventricular ring reentry in embryonic mouse hearts.

Background: During development, AV conduction switches from base-to-apex to apex-to-base conduction after emergence of the conduction system. We hypothesize that after this transition, the bulk of the AV ring, although no longer required for AV conduction, remains transiently able to conduct, providing a potential arrhythmia substrate. We studied AV conduction during this transition and its sensitivity to autonomic modulation.

Intracellular calcium cycling, early afterdepolarizations, and reentry in simulated long QT syndrome.

Objectives: The purpose of this study was to investigate interactions between early afterdepolarizations (EADs) and reentry in long QT (LQT) syndromes.

Background: EADs, a characteristic feature of congenital and acquired LQT syndromes, are classically bradycardia dependent. Mechanisms by which they promote tachyarrhythmias such as torsades de pointes and ventricular fibrillation are not fully understood.

Metabolic inhibition alters subcellular calcium release patterns in rat ventricular myocytes: implications for defective excitation-contraction coupling during cardiac ischemia and failure.

Metabolic inhibition (MI) contributes to contractile failure during cardiac ischemia and systolic heart failure, in part due to decreased excitation-contraction (E-C) coupling gain. To investigate the underlying mechanism, we studied subcellular Ca2+ release patterns in whole cell patch clamped rat ventricular myocytes using two-dimensional high-speed laser scanning confocal microscopy. In cells loaded with the Ca2+ buffer EGTA (5 mmol/L) and the fluorescent Ca2+-indicator fluo-3 (1 mmol/L), depolarization from -40 to 0 mV elicited a striped pattern of Ca2+ release.

Coexistence of two types of ventricular fibrillation during acute regional ischemia in rabbit ventricle.

Introduction: We previously reported that a normal ventricle can demonstrate two types of ventricular fibrillation (VF), depending on the underlying electrophysiologic characteristics at the time of VF induction. We hypothesize that the two types of VF can coexist in acutely ischemic ventricles.

Methods And Results: Optical mapping studies were performed with di-4ANEPPS in 15 Langendorff-perfused rabbit hearts.

Intracellular Ca dynamics in ventricular fibrillation.

In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionally coupled, so that ionic membrane currents regulate Cai cycling and Cai affects ionic currents regulating action potential duration (APD). Although Cai reliably and consistently tracks Vm at normal heart rates, it is possible that at very rapid rates, sarcoplasmic reticulum Cai cycling may exhibit intrinsic dynamics. Non-voltage-gated Cai release might cause local alternations in APD and refractoriness that influence wavebreak during ventricular fibrillation (VF).

Spatiotemporal correlation between phase singularities and wavebreaks during ventricular fibrillation.

Unlabelled: Phase Singularity and Wavebreak.

Introduction: Phase maps and the detection of phase singularities (PSs) have become a well-developed method for characterizing the organization of ventricular fibrillation (VF). How precisely PS colocalizes with wavebreak (WB) during VF, however, is unknown.

Frequency analysis of ventricular fibrillation in Swine ventricles.

It has been suggested from frequency analysis that cardiac fibrillation is driven by stable intramural reentry, with wavebreak occurring due to failure of 1:1 propagation. We tested this hypothesis with a combined experimental and theoretical approach. Optical mapping was performed on epicardial, endocardial, and transmural cut surfaces of fibrillating swine ventricles.