The voltage-sensitive dye di-4-ANEPPS slows conduction velocity in isolated guinea pig hearts

Abstract

BACKGROUND Voltage-sensitive dyes are important tools for mapping electrical activity in the heart. However, little is known about the effects of voltage-sensitive dyes on cardiac electrophysiology. OBJECTIVE To test the hypothesis that the voltage-sensitive dye di-4-ANEPPS modulates cardiac impulse propagation. METHODS Electrical and optical mapping experiments were performed in isolated Langendorff perfused guinea pig hearts. The effect of di-4-ANEPPS on conduction velocity and anisotropy of propagation was quantified. HeLa cells expressing connexin 43 were used to evaluate the effect of di-4-ANEPPS on gap junctional conductance. RESULTS In electrical mapping experiments, di-4-ANEPPS (7.5 μM) was found to decrease both longitudinal and transverse conduction velocities significantly compared with control. No change in the anisotropy of propagation was observed. Similar results were obtained in optical mapping experiments. In these experiments, the effect of di-4-ANEPPS was dose dependent. di-4-ANEPPS had no detectable effect on connexin 43–mediated gap junctional conductance in transfected HeLa cells. CONCLUSION Our results demonstrate that the voltage-sensitive dye di-4-ANEPPS directly and dose-dependently modulates cardiac impulse propagation. The effect is not likely mediated by connexin 43 inhibition. Our results highlight an important caveat that should be taken into account when interpreting data obtained using di-4-ANEPPS in cardiac preparations.

Diverse Fibrosis Architecture and Premature Stimulation Facilitate Initiation of Reentrant Activity Following Chronic Atrial Fibrillation

“…We measured conduction velocity transverse and longitudinal to the generalized fiber orientation for an S1 of 400 milliseconds, and during an S2 of 160 milliseconds. Conduction velocity was quantified with a previously validated algorithm that can distinguish between transverse and longitudinal conduction . In brief, this algorithm creates an isochrone map based on the activation times from the electrograms on the plaque.…”

Voltage sensitive dye di-4-ANNEPS prolongs impulse conduction through ventricles, but not through AV node in isolated rabbit heart

“…There is an evidence for influence of di-4-ANEPPS on cardiac impulse conduction through heart ventricles as well as 1167 A V node in various animal models. Slowing of the conduction velocity in longitudinal as well as transversal direction was described in isolated guinea pig heart [4]. In rat heart, influence of the di-4-ANEPPS on conduction through A V node as well as conduction through the ventricles was observed.…”

“…Nevertheless, the exact mechanisms of influencing cardiac impulse generation or its spreading through the heart tissue in the presence of di-4-ANEPPS are still not known. The slowing of cardiac impulse propagation in isolated guinea pig heart under di-4-ANEPPS was described by Larsen et al [4]. PQ interval prolongation and transient block of atrioventricular conduction in rat heart were reported by Nygren et al [5].…”

Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia

“…In addition, this method eliminates the need for voltage‐sensitive dyes and electromechanical uncouplers or other methods to reduce the contraction of the heart as required for optical mapping techniques. Di‐4‐ANEPPS, a commonly used dye in optical mapping studies, has been shown to alter cardiac electrophysiology, including prolongation of the PQ interval and QRS duration, and reduction of conduction velocity (Nygren et al 2003; Larsen et al 2010, 2012). Likewise, excitation–contraction uncouplers, such as 2,3‐butanedione monoxime, cytochalasin D and diacetyl monoxime, frequently used for optical mapping have been shown to have effects on action potential duration, conduction velocity, electrical restitution curve, calcium transient and ventricular fibrillation activation patterns (Qin et al 2003; Baker et al 2004; Cheng et al 2004; Kettlewell et al 2004).…”