Gap junctional communication controls the overall endothelial calcium response to vasoactive agonists

Kameritsch, Petra; Pogoda, Kristin; Ritter, Angela; Münzing, Silvia; Pohl, Ulrich

doi:10.1093/cvr/cvr345

Cited by 28 publications

(41 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The SMC tone is further controlled by Ca 2+ signaling in ECs, which is also modulated by both Cx40 and Cx37. 15,16 The physiological relevance of these observations is supported by the findings that the renin-dependent hypertension increases the expression of Cx40 in ECs, as well as that of Cx37 and Cx43 in SMCs, via an angiotensin II-dependent mechanism. 13 To assess the relative importance of Cx signaling on renin secretion and vasomotor function, a previous study has investigated the deletion of Cx40 in either RSCs or ECs, using the Cre-lox technology.…”

mentioning

confidence: 82%

Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice

et al. 2014

View full text Add to dashboard Cite

Abstract-Connexin 40 (Cx40) is expressed by the renin-producing cells (RSCs) of the kidneys and the endothelial cells of blood vessels. Cx40 null mice (Cx40 −/− ) feature a much increased renin synthesis and secretion, which results in chronic hypertension, and also display an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels and nitric oxide production. To discriminate the effect of Cx40 in renin secretion and vascular signaling, we targeted Cx40 to either the RSCs or the endothelial cells of Cx40 null mice. When compared with Cx40 −/− controls, the animals expressing Cx40 in RSCs were less hypertensive and featured reduced renin levels, still numerous RSCs outside the wall of the afferent arterioles. In contrast, mice expressing Cx40 in the endothelial cells were as hypertensive as Cx40 −/− mice, in spite of control levels of Cx37 and eNOS. Our data show that blood pressure is improved by restoration of Cx40 expression in RSCs but not in endothelial cells, stressing the prominent role of renin in the mouse hypertension linked to

show abstract

mentioning

confidence: 82%

Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Gap junctions (GJ) allow direct communication between cells by the exchange of ions and small signaling molecules like cyclic nucleotides [9]. Gap junctional communication (GJC) occurs between endothelial [10,11], as well as between smooth muscle cells [11-14]. In small vessels, gap junctions also connect endothelial and smooth muscle cells (myoendothelial gap junctional communication, MEGJC).…”

Section: Introductionmentioning

confidence: 99%

NO, via its target Cx37, modulates calcium signal propagation selectively at myoendothelial gap junctions

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundGap junctional calcium signal propagation (transfer of calcium or a calcium releasing messenger via gap junctions) between vascular cells has been shown to be involved in the control of vascular tone. We have shown before that nitric oxide (NO) inhibits gap junctional communication in HeLa cells exclusively expressing connexin 37 (HeLa-Cx37) but not in HeLa-Cx40 or HeLa-Cx43. Here we studied the effect of NO on the gap junctional calcium signal propagation in endothelial cells which, in addition to Cx37, also express Cx40 and Cx43. Furthermore, we analyzed the impact of NO on intermuscle and on myoendothelial gap junction-dependent calcium signal propagation. Since specific effects of NO at one of these three junctional areas (interendothelial/ myoendothelial/ intermuscle) may depend on a differential membrane localization of the connexins, we also studied the distribution of the vascular connexins in small resistance arteries.ResultsIn endothelial (HUVEC) or smooth muscle cells (HUVSMC) alone, NO did not affect gap junctional Ca2+ signal propagation as assessed by analyzing the spread of Ca2+ signals after mechanical stimulation of a single cell. In contrast, at myoendothelial junctions, it decreased Ca2+ signal propagation in both directions by about 60% (co-cultures of HUVEC and HUVSMC). This resulted in a longer maintenance of calcium elevation at the endothelial side and a faster calcium signal propagation at the smooth muscle side, respectively. Immunohistochemical stainings (confocal and two-photon-microscopy) of cells in co-cultures or of small arteries revealed that Cx37 expression was relatively higher in endothelial cells adjoining smooth muscle (culture) or in potential areas of myoendothelial junctions (arteries). Accordingly, Cx37 - in contrast to Cx40 - was not only expressed on the endothelial surface of small arteries but also in deeper layers (corresponding to the internal elastic lamina IEL). Holes of the IEL where myoendothelial contacts can only occur, stained significantly more frequently for Cx37 and Cx43 than for Cx40 (endothelium) or Cx45 (smooth muscle).ConclusionNO modulates the calcium signal propagation specifically between endothelial and smooth muscle cells. The effect is due to an augmented distribution of Cx37 towards myoendothelial contact areas and potentially counteracts endothelial Ca2+ signal loss from endothelial to smooth muscle cells. This targeted effect of NO may optimize calcium dependent endothelial vasomotor function.

show abstract

“…In line with the work of Berra-Romani et al [29], our results show homogenous endothelial Ca 2+ signaling in response to ATP stimulation. In contrast to these results, Kameritsch et al, recently reported heterogeneous Ca 2+ responses to ATP and demonstrated a role for endothelial gap junctions in the spreading of Ca 2+ signaling in response to ATP stimulation [30]. This discrepancy could be due to differences in ATP concentrations used to stimulate endothelial cells or in the portion of the aorta used to perform the experiments.…”

Section: Discussionmentioning

confidence: 87%

Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca²⁺Signaling in Mouse Aortic Endothelium

Boittin¹,

Alonso²,

Gal³

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Smooth muscle tone is controlled by Ca²⁺ signaling in the endothelial layer. Mouse endothelial cells are interconnected by gap junctions made of Connexin40 (Cx40) and Cx37, which allow the exchange of signaling molecules to coordinate their activity. Here, we investigated the role of Cx40 in the endothelial Ca²⁺ signaling of the mouse aorta. Methods: Ca²⁺ imaging was performed on intact aortic endothelium from both wild type (Cx40+/+) and Connexin40-deficient (Cx40 -/-) mice. Results: Acetylcholine (ACh) induced early fast and high amplitude Ca²⁺ transients in a fraction of endothelial cells expressing the M3 muscarinic receptors. Inhibition of intercellular communication using carbenoxolone or octanol fully blocked the propagation of ACh-induced Ca²⁺ transients toward adjacent cells in WT and Cx40-/- mice. As compared to WT, Cx40-/- mice displayed a reduced propagation of ACh-induced Ca²⁺ waves, indicating that Cx40 contributes to the spreading of Ca²⁺ signals. The propagation of those Ca²⁺ responses was not blocked by suramin, a blocker of purinergic ATP receptors, indicating that there is no paracrine effect of ATP release on the Ca²⁺ waves. Conclusions: Altogether our data show that Cx40 and Cx37 contribute to the propagation and amplification of the Ca²⁺ signaling triggered by ACh in endothelial cells expressing the M3 muscarinic receptors.

show abstract

Gap junctional communication controls the overall endothelial calcium response to vasoactive agonists

Abstract: The global Ca(2+)(i) response of the endothelium to agonists is determined decisively by the functionality of GJs, thus establishing a new role for GJs in controlling endothelial activity and vasomotor function.

Cited by 28 publications

References 35 publications

Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice

Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice

NO, via its target Cx37, modulates calcium signal propagation selectively at myoendothelial gap junctions

Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca²⁺Signaling in Mouse Aortic Endothelium

Contact Info

Product

Resources

About

Gap junctional communication controls the overall endothelial calcium response to vasoactive agonists

Abstract: The global Ca(2+)(i) response of the endothelium to agonists is determined decisively by the functionality of GJs, thus establishing a new role for GJs in controlling endothelial activity and vasomotor function.

Cited by 28 publications

References 35 publications

Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice

Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice

NO, via its target Cx37, modulates calcium signal propagation selectively at myoendothelial gap junctions

Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca2+Signaling in Mouse Aortic Endothelium

Contact Info

Product

Resources

About

Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca²⁺Signaling in Mouse Aortic Endothelium