Interstitial volume modulates the conduction velocity-gap junction relationship

Veeraraghavan R, Salama ME, Poelzing S. Interstitial volume modulates the conduction velocity-gap junction relationship. Am J Physiol Heart Circ Physiol 302: H278-H286, 2012. First published October 21, 2011; doi: 10.1152/ajpheart.00868.2011.-Cardiac conduction through gap junctions is an important determinant of arrhythmia susceptibility. Yet, the relationship between degrees of G(j) uncoupling and conduction velocity (theta) 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 G(j). Interstitial volume (V-IS) was quantified histologically from guinea pig right ventricle. Optical mapping was used to quantify conduction velocity and anisotropy (AR(theta)). Albumin (4 g/l) decreased histologically assessed V-IS, increased transverse theta by 71 +/- 10%, and lowered AR(theta). Furthermore, albumin did not change isolated cell size. Conversely, mannitol increased V-IS, decreased transverse theta by 24 +/- 4%, and increased AR(theta). 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 theta-G(j) relationship was assessed using the G(j) uncoupler carbenoxolone (CBX). Whereas 13 mu M CBX did not significantly affect theta during control, it slowed transverse theta by 38 +/- 9% during mannitol (edema). These data suggest changes in V-IS modulate theta, AR theta, and the theta-Gj relationship and thereby alter arrhythmia susceptibility. Therefore, V-IS may underlie arrhythmia susceptibility, particularly in diseases associated with gap junction remodeling.