scholarly journals Bile canaliculi contract autonomously by releasing calcium into hepatocytes via mechanosensitive calcium channel

2018 ◽  
Author(s):  
Kapish Gupta ◽  
Ng Inn Chuan ◽  
Binh P. Nguyen ◽  
Lisa Tucker-Kellogg ◽  
Boon Chuan Low ◽  
...  

AbstractBile canaliculi (BC) are the smallest vessels of the biliary tree. They are formed from the apical surfaces of adjoining hepatocytes, resulting in lumenal conduits for bile flow. Bile is propelled along the BC by hepatocyte contractions that arise from cyclic waves of apico-basal Ca2+, but the source and regulation of Ca2+ has been unclear. We report that BC contraction correlates with cyclic transfer of Ca2+ from BC lumen to apico-basal Ca2+ waves in adjacent hepatocytes, and does not correlate with endoplasmic reticulum Ca2+. BC contractility was triggered by ionophore A23187 and unaffected by Thapsigargin. The cycles of Ca2+ transfer could be blocked by the mechanosensitive calcium channel inhibitor GsMTx-4, resulting in cholestatic generation of BC-derived vesicles. The mechanosensitive calcium channel Piezo-1 is preferentially localized at BC membranes, and its hyper-activation by Yoda1 causes increased Ca2+ transfer and increased BC contractility. We propose that canaliculi achieve biomechanical homeostasis through the following feedback system: the pressure of accumulated bile is sensed by mechanosensitive channel, which transmit biliary calcium into adjacent hepatocytes for contraction of the BC lumen and propulsion of the bile.

Author(s):  
M. A. Shorikov ◽  
O. N. Sergeeva ◽  
M. G. Lapteva ◽  
N. A. Peregudov ◽  
B. I. Dolgushin

Proximal extrahepatic bile ducts are the biliary tree segment within formal boundaries from cystic ductcommon hepatic duct junction to sectoral hepatic ducts. Despite being a focus of attention of diagnostic and interventional radiologists, endoscopists, hepatobiliary surgeons and transplantologists they weren’t comprehensively described in available papers. The majority of the authors regard bile duct confluence as a group of merging primitively arranged tubes providing bile flow. The information on the proximal extrahepatic bile duct embryonal development, variant anatomy, innervation, arterial, venous and lymphatic supply is too general and not detailed. The present review brought together and systemized exiting to the date data on anatomy and function of this biliary tract portion. Unique, different from the majority of hollow organs organization of the proximal extrahepatic bile duct adapts them to the flow of the bile, i.e. viscous aggressive due to pH about 8.0 and detergents fluid, under higher wall pressure than in other parts of biliary tree. 


2019 ◽  
Vol 10 (3) ◽  
pp. 284-291 ◽  
Author(s):  
Shyam Menon ◽  
Andrew Holt

Cholangiopathies describe a group of conditions affecting the intrahepatic and extrahepatic biliary tree. Impairment to bile flow and chronic cholestasis cause biliary inflammation, which leads to more permanent damage such as destruction of the small bile ducts (ductopaenia) and biliary cirrhosis. Most cholangiopathies are progressive and cause end-stage liver disease unless the physical obstruction to biliary flow can be reversed. This review considers large-duct cholangiopathies, such as primary sclerosing cholangitis, ischaemic cholangiopathy, portal biliopathy, recurrent pyogenic cholangitis and Caroli disease.


1990 ◽  
Vol 259 (5) ◽  
pp. G736-G744 ◽  
Author(s):  
R. Lenzen ◽  
V. J. Hruby ◽  
N. Tavoloni

The present studies were carried out to clarify the mechanism of glucagon choleresis in guinea pigs. At the infusion rate of 1.4 nmol.min-1.kg-1, glucagon increased bile flow from 206.6 +/- 14.3 to 302.6 +/- 35.0 microliters.min-1.kg-1 and bicarbonate biliary concentration from 63.7 +/- 4.2 to 75.5 +/- 5.9 meq/l. Measurements of bile acid excretion in bile, the biliary tree volume, and of the hormone choleretic effect in guinea pigs with proliferated bile ductules/ducts induced by alpha-naphthylisothiocyanate feeding indicated that glucagon, unlike secretin, stimulated canalicular bile flow. Inhibition of prostaglandin synthesis by indomethacin administration (5 mg.kg-1.h-1) did not modify the choleretic effect of glucagon, and infusion of a glucagon analogue (TH-glucagon, 1.4 nmol.min-1.kg-1), which did not increase hepatic formation of adenosine 3'5'-cyclic monophosphate (cAMP), failed to stimulate bile flow. Like the parent hormone, however, TH-glucagon augmented plasma glucose levels and stimulated formation of inositol phosphates. Colchicine pretreatment (0.5 mg/kg ip) almost entirely prevented the choleretic effect of glucagon but did not modify spontaneous and bile acid-induced bile flow and the stimulatory effect of the hormone on glucose release and on hepatic formation of cAMP and inositol phosphates. Finally, glucagon produced a large increase in the biliary entry of horseradish peroxidase, even though this effect was transient and was not coupled to the increase in bile flow. These results indicate that glucagon choleresis in the guinea pig is not secondary to prostaglandin release, is canalicular in origin, involves bicarbonate secretion, is mediated by cAMP, and requires an intact microtubular system.


1991 ◽  
Vol 113 (5) ◽  
pp. 1069-1080 ◽  
Author(s):  
N Watanabe ◽  
N Tsukada ◽  
C R Smith ◽  
M J Phillips

Modern fluorescence microscopic techniques were used to image the bile canalicular system in the intact rat liver, in vivo. By combining the use of sodium fluorescein secretion into bile, with digitally enhanced fluorescence microscopy and time-lapse video, it was possible to capture and record the canalicular motility events that accompany the secretion of bile in life. Active bile canalicular contractions were found predominantly in zone 1 (periportal) hepatocytes of the liver. The contractile movements were repetitive, forceful, and appeared unidirectional moving bile in a direction towards the portal bile ducts. Contractions were not seen in the network of canaliculi on the surface of the liver. Cytochalasin B administration resulted in reduced canalicular motility, progressive dilation of zone 1 canaliculi, and impairment of bile flow. Canalicular dilations invariably involved the branch points of the canalicular network. The findings add substantively to previous in vitro studies using couplets, and suggest that canalicular contractions contribute physiologically to bile flow in the liver.


Meat Science ◽  
2016 ◽  
Vol 115 ◽  
pp. 34-40 ◽  
Author(s):  
Bing Guo ◽  
Wangang Zhang ◽  
Ron K. Tume ◽  
Nicholas J. Hudson ◽  
Feng Huang ◽  
...  

Biomaterials ◽  
2020 ◽  
Vol 259 ◽  
pp. 120283
Author(s):  
Kapish Gupta ◽  
Inn Chuan Ng ◽  
Gowri Manohari Balachander ◽  
Binh P. Nguyen ◽  
Lisa Tucker-Kellogg ◽  
...  

1991 ◽  
Vol 260 (1) ◽  
pp. G167-G174
Author(s):  
W. G. Hardison ◽  
E. Dalle-Molle ◽  
E. Gosink ◽  
P. J. Lowe ◽  
J. H. Steinbach ◽  
...  

To determine the effects of alteration of biliary paracellular permeability on bile flow and composition, we measured the biliary outputs of compounds highly concentrated in bile, all infused at a constant rate in the isolated rat liver perfused with Krebs-Henseleit buffer in a one-pass fashion. Paracellular permeability was increased by infusing 10(-8) M vasopressin (VP). The cholephilic compounds were three cations of various molecular weights, tributylmethylammonium (TBuMA), N-acetylprocainamide ethobromide (APAEB), and propidium iodide, and two anions, taurocholate (TC), a micelle-forming bile acid, and taurodehydrocholate (TDHC), an nonmicelle former. When TC was infused and paracellular permeability increased with VP, neither bile flow nor TC output changed, whereas outputs of cations fell. When TDHC was infused, TDHC output fell, as did outputs of all cations. The decrements in cation outputs exceeded that of TDHC and were inversely related to the molecular weight of the cation. To document that these changes were not related to reduced uptake of these compounds, we tested the uptakes of TBuMA, APAEB, and TDHC into isolated hepatocytes. In no case did 10(-8) M VP significantly reduce uptake. The data demonstrate that micelle-forming bile acids, with their high effective molecular weights, do not efflux from the biliary tree when permeability is increased with VP, whereas nonmicelle-forming bile acids do. Cations efflux more readily than anions, and within this group efflux rate is inversely related to molecular weight. The data confirm the size and charge selectivity of biliary tree permeability.(ABSTRACT TRUNCATED AT 250 WORDS)


1983 ◽  
Vol 245 (5) ◽  
pp. G651-G655 ◽  
Author(s):  
J. Reichen ◽  
M. Le

To determine whether bile salts alter the permeability of the biliary tree to inert solutes, we investigated the effects of taurocholate and taurodehydrocholate on [14C]sucrose bile-to-plasma ratio in the situ perfused rat liver. Sucrose bile-to-plasma ratio remained virtually constant over a 3-h period in untreated rats. Infusing increasing amounts of taurocholate produced the anticipated dose-dependent increase in bile flow and bile salt secretion up to a maximal secretory rate of 278 nmol X min-1 X g liver-1. When the secretory rate was exceeded, bile flow decreased by 22%. Even at doses below the maximal secretory rate, sucrose bile-to-plasma ratio increased in a dose-dependent fashion. To determine whether this was due to recruitment of more permeable centrizonal hepatocytes, the effect of equimolar amounts of taurodehydrocholate was determined. This nonmicelle-forming bile salt led to more marked choleresis than taurocholate but did not affect sucrose bile-to-plasma ratio. We conclude that taurocholate, but not taurodehydrocholate, leads to a dose-dependent increase in biliary permeability.


1982 ◽  
Vol 242 (4) ◽  
pp. G319-G325 ◽  
Author(s):  
J. S. Reed ◽  
N. D. Smith ◽  
J. L. Boyer

In the isolated perfused liver of the little skate, Raja erinacea, bile flow averaged 5.07 +/- 0.58 (mean +/- SE) microliters.h-1.g liver-1 in 21 experiments at a perfusion pressure of 5.0 cm Ringer compared to 3.79 +/- 0.32 in 38 experiments at 2.5 cm (P less than 0.05). [14C]inulin readily entered skate bile. Bile-to-plasma [14C]inulin ratios corrected for delay in transit time, averaged 0.46 +/- 0.07 at 1 h and rose to 0.74 +/- 0.06 by 4 h, although bile flow remained constant. In experiments in which [14C]inulin reached equilibrium between bile and plasma, the bile-to-plasma ratio conformed to the theoretical relationship between bile flow, solvent drag, and inert solute diffusion predicted at extremely low bile flows, but demonstrated that the skate biliary tree is more permeable to inulin than that of the rat. Electron microscopic studies demonstrated that ionic lanthanum could traverse the tight junctions. However, freeze-fracture studies of junction structure did not differ qualitatively from similar studies in the rat. Partial dependence of bile flow on perfusion pressure, high bile-to-plasma inulin ratios, and permeability of the canalicular tight junctions to ionic lanthanum all suggest that the paracellular pathway may be an important component of bile formation in the skate.


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