Improved propagation in myometrium associated with gap junctions during parturition

1989 ◽  
Vol 256 (1) ◽  
pp. C130-C141 ◽  
Author(s):  
S. M. Miller ◽  
R. E. Garfield ◽  
E. E. Daniel

The hypothesis that gap junction (GJ) formation between myometrial cells at term improves electrical coupling was tested. We measured the spread of electrical excitation from six extracellular electrodes aligned on uterine strips in either the longitudinal (axial) or transverse (circumferential) direction. Spontaneous bursts propagated over the entire 15-mm recording distance in the axial direction at both preterm and parturition and showed some characteristics of a system of coupled relaxation oscillators. However, individual spikes within the bursts propagated further and with higher velocity at parturition than at preterm. In the circumferential direction, both bursts and individual spikes propagated further at parturition than before. Propagation in this axis at parturition appeared to require an intact circular muscle layer. Spikes evoked by electrical stimulation also propagated further and with higher velocity in both axes at parturition. Electron microscopy showed many GJs between uterine smooth muscle cells during parturition, but few and sometimes no GJs at preterm. Thus improved propagation was associated with increased GJ contact between myometrial cells, consistent with the hypothesis that gap junction formation at term improves electrical coupling.

1991 ◽  
Vol 260 (3) ◽  
pp. G390-G398 ◽  
Author(s):  
F. Vogalis ◽  
S. M. Ward ◽  
K. M. Sanders

Electrical slow waves decay in amplitude as they conduct from the myenteric to the submucosal regions of the circular muscle layer in the canine pyloric sphincter. We used the partitioned chamber method to study the passive and active properties of pyloric muscles, and we found that length constants of circular muscles of myenteric region were significantly longer than muscles near the submucosal surface. These data suggested differences in either membrane resistance, junctional resistance, or cytoplasmic resistance. The first parameter was evaluated by measuring time constants in intact tissues and single cells isolated from the submucosal and myenteric regions. Membrane time constants were not different in the two regions, nor were differences found in the input resistances of isolated cells. Morphological studies failed to demonstrate differences in cell diameters in the two regions suggesting that cytoplasmic resistances are similar. These findings suggest that the different cable properties in the two regions may be due to differences in electrical coupling. Morphological examination revealed similar numbers of gap junctions between cells in the two regions, but large differences were noted in the size of muscular bundles. Muscles of the myenteric region were arranged into large, tightly packed bundles, whereas muscles of the submucosal region consisted of small bundles with an extensive extracellular space filled with connective tissue. We suggest that the difference in cable properties may be due to differences in electrical coupling between bundles. These data suggest that submucosal muscles function more like a multiunit smooth muscle, whereas myenteric muscles behave as a single unit.


1979 ◽  
Vol 57 (6) ◽  
pp. 578-580 ◽  
Author(s):  
Elane Zelcer ◽  
E. E. Daniel

Two distinct layers of circular muscle have previously been demonstrated in dog jejunum, the main circular layer containing many gap junction contacts, and an inner dense muscle layer where no gap junctions have been found. Length constants were determined for these muscle layers and no significant difference was found between these values. The main circular muscle cells had lower membrane potentials and may have had abnormally low space constants owing to injury. It was concluded that the absence of gap junctions in the inner dense layer does not reduce the spread of passive current as might be expected of electrically isolated cells, and it is suggested that an alternate pathway for passive current exists in this layer.


1982 ◽  
Vol 80 (3) ◽  
pp. 353-375 ◽  
Author(s):  
S M Sims ◽  
E E Daniel ◽  
R E Garfield

We have studied some passive electrical properties of uterine smooth muscle to determine whether a change in electrical parameters accompanies gap junction formation at delivery. The length constant of the longitudinal myometrium increased from 2.6 +/- 0.8 mm (X +/- SD) before term to 3.7 +/- 1 mm in tissues from delivering animals. The basis of the change was a 33% decrease in internal resistance and a 46% increase in membrane resistance. Axial current flow in an electrical syncytium such as myometrium is impeded by the cytoplasm of individual cells plus the junctions between cells. Measurement of the longitudinal impedance indicated that the specific resistance of the myoplasmic component was constant at 319 +/- 113 omega . cm before term and 340 +/- 93 omega . cm at delivery. However, a decrease in junctional resistance was apparent from 323 +/- 161 omega . cm to 134 +/- 64 omega . cm at delivery. 1.5-2 d after delivery, the junctional resistance was increased, as was the myoplasmic resistance. Thin-section electron microscopy of some of the same muscle samples showed that gap junctions were present in significantly greater numbers in the delivering tissues. Therefore, our results support the hypothesis that gap junction formation at delivery is associated with improved electrical coupling of uterine smooth muscle.


Biomaterials ◽  
2006 ◽  
Vol 27 (27) ◽  
pp. 4765-4774 ◽  
Author(s):  
Yuji Haraguchi ◽  
Tatsuya Shimizu ◽  
Masayuki Yamato ◽  
Akihiko Kikuchi ◽  
Teruo Okano

1990 ◽  
Vol 259 (3) ◽  
pp. C402-C408 ◽  
Author(s):  
E. P. Burke ◽  
K. M. Sanders

Previous studies have suggested that the membrane potential gradient across the circular muscle layer of the canine proximal colon is due to a gradient in the contribution of the Na(+)-K(+)-ATPase. Cells at the submucosal border generate approximately 35 mV of pump potential, whereas at the myenteric border the pump contributes very little to resting potential. Results from experiments in intact muscles in which the pump is blocked are somewhat difficult to interpret because of possible effects of pump inhibitors on membrane conductances. Therefore, we studied isolated colonic myocytes to test the effects of ouabain on passive membrane properties and voltage-dependent currents. Ouabain (10(-5) M) depolarized cells and decreased input resistance from 0.487 +/- 0.060 to 0.292 +/- 0.040 G omega. The decrease in resistance was attributed to an increase in K+ conductance. Studies were also performed to measure the ouabain-dependent current. At 37 degrees C, in cells dialyzed with 19 mM intracellular Na+ concentration [( Na+]i), ouabain caused an inward current averaging 71.06 +/- 7.49 pA, which was attributed to blockade of pump current. At 24 degrees C or in cells dialyzed with low [Na+]i (11 mM), ouabain caused little change in holding current. With the input resistance of colonic cells, pump current appears capable of generating at least 35 mV. Thus an electrogenic Na+ pump could contribute significantly to membrane potential.


2004 ◽  
Vol 86 (2) ◽  
pp. 781-796 ◽  
Author(s):  
Derek L. Beahm ◽  
James E. Hall

2006 ◽  
Vol 290 (6) ◽  
pp. G1307-G1317 ◽  
Author(s):  
Ling Cheng ◽  
Weibiao Cao ◽  
Claudio Fiocchi ◽  
Jose Behar ◽  
Piero Biancani ◽  
...  

Platelet-activating factor (PAF) and interleukin-6 (IL-6) are produced in the esophagus in response to HCl and affect ACh release, causing changes in esophageal motor function similar to esophagitis (Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289: G418–G428, 2005). We therefore examined HCl-activated mechanisms for production of PAF and IL-6 in cat esophageal mucosa and circular muscle. A segment of normal mucosa was tied at both ends, forming a mucosal sac (Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289: G860–G869, 2005) that was filled with acidic Krebs buffer (pH 5.8) or normal Krebs buffer (pH 7.0) as control and kept in oxygenated Krebs buffer for 3 h. The supernatant of the acidic sac (MS-HCl) abolished contraction of normal muscle strips in response to electric field stimulation. The inhibition was reversed by the PAF antagonist CV3988 and by IL-6 antibodies. PAF and IL-6 levels in MS-HCl and mucosa were significantly elevated over control. IL-6 levels in mucosa and supernatant were reduced by CV3988, suggesting that formation of IL-6 depends on PAF. PAF-receptor mRNA levels were not detected by RT-PCR in normal mucosa, but were significantly elevated after exposure to HCl, indicating that HCl causes production of PAF and expression of PAF receptors in esophageal mucosa and that PAF causes production of IL-6. PAF and IL-6, produced in the mucosa, are released to affect the circular muscle layer. In the circular muscle, PAF causes production of additional IL-6 that activates NADPH oxidase to induce production of H2O2. H2O2 causes formation of IL-1β that may induce production of PAF in the muscle, possibly closing a self-sustaining cycle of production of inflammatory mediators.


1976 ◽  
Vol 22 (2) ◽  
pp. 427-434
Author(s):  
F. Mazet ◽  
J. Cartaud

The freeze-fracturing technique was used to characterize the junctional devices involved in the electrical coupling of frog atrial fibres. These fibres are connected by a type of junction which can be interpreted as a morphological variant of the “gap junction” or “nexus”. The most characteristic features are rows of 9-nm junctional particles forming single or anastomosed circular profiles on the inner membrane face, and corresponding pits on the outer membrane face. Very seldom aggregates consisting of few geometrically disposed 9-nm particles are found. The significance of the junctional structures in the atrial fibres is discussed, with respect to present knowledge about junctional features of gap junctions in various tissues, including embryonic ones.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
James W Smyth ◽  
Jose M Sanchez ◽  
Samy Lamouille ◽  
Ting-Ting Hong ◽  
Jacob M Vogan ◽  
...  

During each heartbeat, robust cell-cell electrical coupling via connexin 43 (Cx43) gap junctions allows billions of individual cardiomyocytes to contract in synchrony. Cx43 turns over rapidly, and altered Cx43 trafficking during disease contributes to the arrhythmias of sudden cardiac death. The overall phosphorylation status of the Cx43 protein is known to regulate gap junction coupling, but the role of many residue specific phosphorylation events remains unknown. One such residue, Ser373, forms a mode-1 14-3-3 binding motif upon phosphorylation. Given that 14-3-3 proteins are known to regulate protein trafficking, we hypothesized a role for Cx43 Ser373 phosphorylation in regulation of Cx43 gap junction coupling. Using Langendorff-perfused mouse hearts we find robust phosphorylation of Cx43 at Ser373 and Ser368 after 30 min of no-flow ischemia. In human cell lines, a S373A mutation ablated Cx43/14-3-3 complexing and 35 S pulse-chase revealed Cx43 S373A also experiences a longer half-life than wild-type Cx43. Previous reports have implicated phosphorylation of Cx43 Ser368 in PKC mediated Cx43 internalization. We find that upon activation of PKC, the Cx43 S373A mutant undergoes lower and more transient levels of phosphorylation at Ser368 than wild-type Cx43. Consistent with these data, siRNA-mediated ablation of 14-3-3 expression results in enlargement of gap junction plaque formation at cell-cell borders. In conclusion, we propose that phosphorylation of Cx43 Ser373 results in 14-3-3 binding which promotes and maintains phosphorylation of Cx43 Ser368 and the subsequent internalization of gap junction channels. These results identify for the first time a specific role for 14-3-3 proteins in regulation of Cx43 internalization during acute ischemia and contribute to the development of therapies aimed at preserving or enhancing gap junction coupling in the heart.


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