scholarly journals Intercellular Conduction Optimizes Arterial Network Function and Conserves Blood Flow Homeostasis During Cerebrovascular Challenges

2020 ◽  
Vol 40 (3) ◽  
pp. 733-750 ◽  
Author(s):  
Anil Zechariah ◽  
Cam Ha T. Tran ◽  
Bjorn O. Hald ◽  
Shaun L. Sandow ◽  
Maria Sancho ◽  
...  
Keyword(s):  
Blood Flow ◽  
Contractile Activity ◽  
Electron Microscopic ◽  
Gap Junctional Communication ◽  
Arterial Network ◽  
Junctional Communication ◽  
Electrical Signaling ◽  
Gap Junctional

Objective: Cerebral arterial networks match blood flow delivery with neural activity. Neurovascular response begins with a stimulus and a focal change in vessel diameter, which by themselves is inconsequential to blood flow magnitude, until they spread and alter the contractile status of neighboring arterial segments. We sought to define the mechanisms underlying integrated vascular behavior and considered the role of intercellular electrical signaling in this phenomenon. Approach and Results: Electron microscopic and histochemical analysis revealed the structural coupling of cerebrovascular cells and the expression of gap junctional subunits at the cell interfaces, enabling intercellular signaling among vascular cells. Indeed, robust vasomotor conduction was detected in human and mice cerebral arteries after focal vessel stimulation: a response attributed to endothelial gap junctional communication, as its genetic alteration attenuated this behavior. Conducted responses were observed to ascend from the penetrating arterioles, influencing the contractile status of cortical surface vessels, in a simulated model of cerebral arterial network. Ascending responses recognized in vivo after whisker stimulation were significantly attenuated in mice with altered endothelial gap junctional signaling confirming that gap junctional communication drives integrated vessel responses. The diminishment in vascular communication also impaired the critical ability of the cerebral vasculature to maintain blood flow homeostasis and hence tissue viability after stroke. Conclusions: Our findings highlight the integral role of intercellular electrical signaling in transcribing focal stimuli into coordinated changes in cerebrovascular contractile activity and expose, a hitherto unknown mechanism for flow regulation after stroke.

scholarly journals Intercellular Conduction Optimizes Arterial Network Function and Conserves Blood Flow Homeostasis during Cerebrovascular Challenges

2019 ◽  
Author(s):  
Anil Zechariah ◽  
Cam Ha T. Tran ◽  
Bjorn O. Hald ◽  
Shaun L. Sandow ◽  
Maria Sancho ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tissue Injury ◽  
Vascular Cells ◽  
Arterial Tree ◽  
Gap Junctional Communication ◽  
Arterial Network ◽  
Junctional Communication ◽  
Electrical Signalling ◽  
Gap Junctional

AbstractCerebral arterial networks match blood flow delivery with neural activity. Neurovascular response begins with a stimulus and a focal change in vessel diameter, which by themselves is inconsequential to blood flow magnitude, until they spread and alter the contractile status of neighboring arterial segments. We sought to define the mechanisms underlying integrated vascular behavior and considered the role of intercellular electrical signalling in this phenomenon. Electron microscopic and histochemical analysis revealed the structural coupling of cerebrovascular cells and the expression of gap junctional subunits at the cell interfaces, enabling intercellular signaling among vascular cells. Indeed, robust vasomotor conduction was detected in human and mice cerebral arteries after focal vessel stimulation; a response attributed to endothelial gap junctional communication, as its genetic alteration attenuated this behavior. Conducted responses was observed to ascend from the penetrating arterioles, influencing the contractile status of cortical surface vessels, in a simulated model of cerebral arterial network. Ascending responses recognised in vivo after whisker stimulation, were significantly attenuated in mice with altered endothelial gap junctional signalling confirming that gap junctional communication drives integrated vessel responses. The diminishment in vascular communication also impaired the critical ability of the cerebral vasculature to maintain blood flow homeostasis and hence tissue viability, after stroke. Our findings establish the integral role of intercellular electrical signalling in transcribing focal stimuli into coordinated changes in cerebrovascular contractile activity and expose, a hitherto unknown mechanism for flow regulation after stroke.SignificanceNeurovascular responses are viewed as a one step process whereby stimuli derived from neural cells focally diffuse to a neighboring vessel, altering its contractile state. While focal changes in tone can subtly tune flow distribution, they can’t substantively change “perfusion magnitude” as vascular resistance is broadly distributed along the cerebral arterial tree. We report that nature overcomes this biophysical constraint by conducting electrical signals among coupled vascular cells, along vessels, and across branch points. Our quantitative exploration of intercellular conduction illustrates how network coordination optimizes blood flow delivery in support of brain function. Diminishing the ability of vascular cells to electrically communicate, mitigates the brain’s ability to regulate perfusion during functional hyperemia and after stroke, the latter advancing tissue injury.

Distribution, propagation, and coordination of contractile activity in lymphatics

1993 ◽  
Vol 264 (4) ◽  
pp. H1283-H1291 ◽  
Author(s):  
D. C. Zawieja ◽  
K. L. Davis ◽  
R. Schuster ◽  
W. M. Hinds ◽  
H. J. Granger
Keyword(s):  
Gap Junction ◽  
Conduction Velocity ◽  
Contractile Activity ◽  
Lymph Flow ◽  
Rat Small Intestine ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Gap Junctional ◽  
Flow Stream

The propagation and coordination of lymphatic contractions were studied in the mesentery of the rat small intestine using in situ microscopic observation. Indexes of lymphatic diameter were simultaneously measured at two adjacent lymphangions in spontaneously contracting lymphatics (n = 51). Diameter index, contraction frequency, and the percentage of the intersegmental contractions that were propagated and coordinated (PP) were determined at both sites. The conduction velocity of the contractile activity and the percentage of the coordinated contractions that were propagated both antegrade to the direction of lymph flow and retrograde to the flow stream were determined. The results indicate that 1) 80-90% of the lymphatic contractions in the vessels we evaluated were propagated, 2) the wave of contractile activity propagated both centrally and peripherally, and 3) the conduction velocity of the contractile activity was approximately 4-8 mm/s. We tested the hypothesis that gap junctional communication is responsible for the coordination of the contractile event. To accomplish this, we used the gap junction blockers n-heptanol and oleic acid. PP was 90 +/- 4% under normal conditions and fell to a minimum value of 55 +/- 7% during the gap junction blockade. These results indicate that gap junctional communication played an important role in the propagation and coordination of contractions that occurred in spontaneously active lymphatics.

Role of gap junctional communication in restitution of rat gastric mucosa

1998 ◽  
Vol 114 ◽  
pp. A302-A303
Author(s):  
N. Takahashi ◽  
T. Joh ◽  
K. Seno ◽  
K. Watanabe ◽  
K. Tsuchida ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Rat Gastric Mucosa ◽  
Gap Junctional

scholarly journals Interaction between Connexin50 and Mitogen-activated Protein Kinase Signaling in Lens Homeostasis

2009 ◽  
Vol 20 (10) ◽  
pp. 2582-2592 ◽  
Author(s):  
Teresa I. Shakespeare ◽  
Caterina Sellitto ◽  
Leping Li ◽  
Clio Rubinos ◽  
Xiaohua Gong ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signal Transduction Pathways ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Mitogen Activated Protein ◽  
Gap Junctional

Both connexins and signal transduction pathways have been independently shown to play critical roles in lens homeostasis, but little is known about potential cooperation between these two intercellular communication systems. To investigate whether growth factor signaling and gap junctional communication interact during the development of lens homeostasis, we examined the effect of mitogen-activated protein kinase (MAPK) signaling on coupling mediated by specific lens connexins by using a combination of in vitro and in vivo assays. Activation of MAPK signaling pathways significantly increased coupling provided by Cx50, but not Cx46, in paired Xenopus laevis oocytes in vitro, as well as between freshly isolated lens cells in vivo. Constitutively active MAPK signaling caused macrophthalmia, cataract, glucose accumulation, vacuole formation in differentiating fibers, and lens rupture in vivo. The specific removal or replacement of Cx50, but not Cx46, ameliorated all five pathological conditions in transgenic mice. These results indicate that MAPK signaling specifically modulates coupling mediated by Cx50 and that gap junctional communication and signal transduction pathways may interact in osmotic regulation during postnatal fiber development.

The role of gap junctions in patterning of the chick limb bud

Development ◽  
1990 ◽  
Vol 108 (4) ◽  
pp. 623-634 ◽  
Author(s):  
F. Allen ◽  
C. Tickle ◽  
A. Warner
Keyword(s):  
Gap Junctions ◽  
Lucifer Yellow ◽  
Limb Bud ◽  
Limb Patterning ◽  
Posterior Limb ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Mesenchyme Cells ◽  
Gap Junctional

The role of gap junctional communication during patterning of the chick limb has been investigated. Affinity-purified antibodies raised against rat liver gap junctional proteins were used to block communication between limb mesenchyme cells. Co-injection of the antibodies and Lucifer yellow into mesenchyme cultures demonstrated that communication was inhibited almost immediately. When antibodies were loaded into mesenchyme tissue by DMSO permeabilization, [3H]nucleotide transfer was prevented for at least 16 h. Polarizing region tissue from the posterior limb bud margin causes digit duplications when grafted to the anterior margin. Quail polarizing region cells were loaded with gap junction antibody and grafted into chick wing buds. The antibody had no effect on growth or survival of the grafted cells. As very few polarizing region cells are required to initiate duplications, the number of polarizing region cells in the grafts was reduced by diluting 1:9 with anterior mesenchyme tissue. When either polarizing region or anterior mesenchyme tissue in the graft was loaded separately with antibody, there was little effect on respecification of the digit pattern. However, loading both tissues in the graft caused a significant decrease in duplications. This indicates that a major role of gap junctions in limb patterning may be to enable polarizing region cells to communicate directly with adjacent anterior mesenchyme. A role for gap junctional communication between anterior mesenchyme cells cannot be excluded. The results are discussed in relation to the role of retinoic acid as a putative morphogen.

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