Heterogeneity In The Distribution Of Vascular Gap Junctions And Connexins: Implications For Function

Abstract

1. Gap junctions, which are comprised of members of a family of membrane proteins called connexins (Cx), permit the transfer of electrical and chemical information between adjacent cells in a wide variety of tissues. The aim of the present study was to compare the expression of Cx37, 40 and 43 in the smooth muscle and endothelium of a large elastic artery and two smaller muscular arteries of the rat. Serial section electron microscopy was also used to determine the presence of pentalaminar gap junctions in the smooth muscle and the incidence of myoendothelial gap junctions between the smooth muscle and endothelial cells in muscular arteries of different size. 2. Using immunohistochemistry, Cx37, 40 and 43 were found in the endothelium of the aorta, caudal and basilar arteries, with Cx43 being the least abundant. Connexin 43 was readily observed throughout the muscle layers of the aorta, but was not detected in the media of the caudal or basilar arteries. Connexin 40 was not detected in the media of any of the arteries, while very fine punctate staining was observed with Cx37 antibodies in the media of the caudal and basilar arteries, but not in the aorta. 3. Real-time polymerase chain reaction showed that the expression of mRNA for Cx43 was 15-fold greater in the aorta than in the caudal artery of the rat. 4. At the ultrastructural level, small pentalaminar gap junctions (< 100 nm) were found between the fine processes of adjacent smooth muscle cells and also between the smooth muscle and endothelial cells. The incidence of myoendothelial gap junctions in the mesenteric vascular bed and in the caudal artery increased as vessel size decreased. 5. In summary, heterogeneity exists within the vascular system with regard to the distribution of gap junctions and their constituent Cx. Such variation will have important consequences for the coordination and propagation of vascular responses. In muscular arteries, in comparison with elastic arteries, Cx37 may be more important than Cx43 for cell coupling within the smooth muscle layers. The correlation between the incidence of myoendothelial gap junctions and the role of endothelium-derived hyperpolarizing factor, relative to nitric oxide, in vasodilatory responses suggests that myoendothelial gap junctions play an important physiological role in the regulation of vascular tone.

Hypertension attenuates cell-to-cell communication in hamster retractor muscle feed arteries

“…Although it is an intriguing hypothesis, others proposed an explanation based on the differential expression of gap junctions between vascular cells (39). In greater detail, past studies have noted that gap junctional expression is far greater between adjacent endothelial cells than between neighboring smooth muscle cells or the two cell layers (10,12,20,21). Such variability would predictably create an environment where the impedance of an endothelial cell would be considerably lower than that of a smooth muscle cell.…”

Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis

“…Gap junction proteins mediate the direct diffusion of signals between adjacent cells (Wagner, 2008). In the microcirculation, gap junction proteins facilitate electrical coupling between endothelial cells (Schmidt et al, 2008), which plays an important role in the regulation of vascular tone (de Wit et al, 2000;Hill et al, 2002). The mechanism underlying arterial-specific regulation of connexins remains unknown.…”

Exocrine specific expression of Connexin32 is dependent on the basic helix-loop-helix transcription factor Mist1

“…Elucidating these regulatory factors is of significant interest since much of the function associated with a specific gap junction complex is dependent on the types and amounts of connexins it contains (Hill et al, 2002;. Expression of the connexin gene family is probably regulated by key transcription factors that exhibit similar patterns of spatial expression.…”