Interstitial volume modulates the conduction velocity-gap junction relationship

Abstract

Cardiac conduction through gap junctions is an important determinant of arrhythmia susceptibility. Yet, the relationship between degrees of Gj uncoupling and conduction velocity (θ) remains controversial. Conflicting results in similar experiments are normally attributed to experimental differences. We hypothesized that interstitial volume modulates conduction velocity and its dependence on Gj. Interstitial volume (VIS) was quantified histologically from guinea pig right ventricle. Optical mapping was used to quantify conduction velocity and anisotropy (ARθ). Albumin (4 g/l) decreased histologically assessed VIS, increased transverse θ by 71 ± 10%, and lowered ARθ. Furthermore, albumin did not change isolated cell size. Conversely, mannitol increased VIS, decreased transverse θ by 24 ± 4%, and increased ARθ. Mannitol also decreased cell width by 12%. Furthermore, mannitol was associated with spontaneous ventricular tachycardias in three of eight animals relative to zero of 15 during control. The θ-Gj relationship was assessed using the Gj uncoupler carbenoxolone (CBX). Whereas 13 μM CBX did not significantly affect θ during control, it slowed transverse θ by 38 ± 9% during mannitol (edema). These data suggest changes in VIS modulate θ, ARθ, and the θ-Gj relationship and thereby alter arrhythmia susceptibility. Therefore, VIS may underlie arrhythmia susceptibility, particularly in diseases associated with gap junction remodeling.