Gap Junctions Suppress Electrical but Not [Ca 2+ ] Heterogeneity in Resistance Arteries

Abstract

Despite stochastic variation in the molecular composition and morphology of individual smooth muscle and endothelial cells, the membrane potential along intact microvessels is remarkably uniform. This is crucial for coordinated vasomotor responses. To investigate how this electrical homogeneity arises, a virtual arteriole was developed that introduces variation in the activities of ion-transport proteins between cells. By varying the level of heterogeneity and subpopulations of gap junctions (GJs), the resulting simulations shows that GJs suppress electrical variation but can only reduce cytosolic [Ca(2+)] variation. The process of electrical smoothing, however, introduces an energetic cost due to permanent currents, one which is proportional to the level of heterogeneity. This cost is particularly large when electrochemically different endothelial-cell and smooth-muscle-cell layers are coupled. Collectively, we show that homocellular GJs in a passively open state are crucial for electrical uniformity within the given cell layer, but homogenization may be limited by biophysical or energetic constraints. Owing to the ubiquitous presence of ion transport-proteins and cell-cell heterogeneity in biological tissues, these findings generalize across most biological fields.

Myoendothelial coupling through Cx40 contributes to EDH‐induced vasodilation in murine renal arteries: evidence from experiments and modelling

“…Computational models of conducted responses have suggested that the conducted response requires that the MEGJ resistance is between 500 MOhms and 5 GOhms. 15,33,34 If the resistance decreases below 500 MOhms, the current that carries the response appears to be diluted out of the EC layer. A resistance of 500 MOhms compares to a radius of 2.2 nm in the present model.…”

“…Signalling between ECs and VSMCs has previously been addressed with mathematical models. Computational models of conducted responses have suggested that the conducted response requires that the MEGJ resistance is between 500 MOhms and 5 GOhms . If the resistance decreases below 500 MOhms, the current that carries the response appears to be diluted out of the EC layer.…”

“…Myograph experiments: All compounds were prepared as stock solutions in water or DMSO (≤ 0.1% in final solution) and diluted in PSS. The different types of inhibitors were administered in amounts to give the following final bath concentrations: Indomethacin 3 lM, L-NAME 300 lM, TRAM- 34…”

Electrical Communication in Lymphangions

“…Parameters were fitted to recorded V m oscillations in a rhythmically contracting lymphangion. In a subset of simulations, a heterogeneous population of LMCs was generated by introducing random values of g l , g Ca , and g K in each LMC using a normal-distributed random generator (17). Model parameters are given in Table 1.…”

“…Yet, higher levels of heterogeneity decrease the dependency of wave speed on stimulation. Without pacemaker cells, the domain of AP waves therefore depends on the level of LMC heterogeneity, which is likely to differ from (and certainly exceed) a 15% Gaussian distribution (17). Lymphatic contraction waves emerge upon sufficient depolarization of the LMC layer, i.e., in the direction of lower-toward-higher levels of depolarization.…”