Disorders of Bile Acid Transport

Bile salts take part in a rather efficient enterohepatic circulation in which most of the secreted bile salts are reclaimed by absorption in the terminal ileum. In the liver the sodium dependent taurocholate transporter (NTCP) at the basolateral (sinusoidal) membrane and the bile salt export pump...

Distribution and Targeting Mechanisms of Voltage Activated Ca2+ Channels

Stefan Herlitze and Melanie D. Mark

Voltage dependent Ca2+ channels control critical parameters of cell function. Their involvement in excitation contraction (EC)-coupling in muscle, their role in secretion in pancreas, their involvement in the acrosome reaction in sperm and their function in fast and slow signal transduction in br...

Drug-induced cholestatic liver disease

Drug induced cholestatic liver disease is a subtype of liver injury that is characterized by predominant elevations of alkaline phosphatase and bilirubin secondary to the administration of a hepatotoxic agent. It can manifest itself as a cholestatic hepatitis or as bland cholestasis, depending...

Exploring the Function and Pharmacotherapeutic of Potential Voltage-Gated Ca2+ Channels with Gene-Knockout Models

Jorg Striessnig and Alexandra Koschak

The importance of the intracellular free Ca2+ concentration as a key cellular signal transduction mechanism requires a tight control of Ca2+ homeostasis thus enabling the independent regulation of free cytosolic Ca2+ levels even within different cellular signaling compartments. In electrically ex...

Fat Absorption and Lipid Metabolism in Cholestasis

The liver has a central role in control of various aspects of lipid metabolism. Primarily, the liver produces bile, constituents of which are required for efficient intestinal fat absorption. Additionally, biliary secretion of cholesterol (either as such, or after metabolism in the form of bil...

Fusome as a Cell-Cell Communication Channel of Drosophila Ovarian Cyst

Jean-René Huynh

In most animal species, female and male gametes are produced within clusters of germ cells which share a common cytoplasm through cell-cell channels. In Drosophila ovaries, these cells synchronise their divisions and specialise one cell of the cluster as the future egg. Both processes are organised ...

Gap Junctions in the Liver

Gap junctions are hexameric hemichannels that are inserted into the plasma membrane and allow for direct exchange of cytosolic contents among adjacent cells. Connexin 26 and connexin 32 are the specific types of gap junctions found in hepatocytes, and connexin 43 is the predominant gap junctio...

Gap Junctions: Cell-Cell Channels in Animals

Fabio Mammano

Gap junctions provide one of the most common forms of intercellular communication. The structures underlying these communicating cell junctions1 were soon resolved in membrane associated particles forming aggregates of six subunits.2 They are composed of membrane proteins that form a channel that is...

Genetic Defects in Biliary Lipid Transport

In terms of solute mass, lipids are the second most important component of bile. Biliary lipids mainly consist of phospholipid (almost exclusively phosphatidylcholine; PC) and cholesterol. The ratio in which these two lipids are secreted varies considerably between species. In rodents th...

Genetics, Mutations and Polymorphisms

Genetic approaches complement functional approaches to the study of hereditary disease, and have contributed substantially to our understanding of the biology of enterohepatic circulation in health and disease. The basic steps in genetic mapping of a disease gene are reviewed here. They includ...

Hepatic Copper Transport

Copper is an essential nutrient that is required in a number of critical metabolic path ways. This metal is absorbed in the stomach and duodenum, stored in the liver and excreted in the bile. The liver functions to maintain copper balance as the amount of copper excreted in the bile is directly...

Hepatic Drug Metabolism

The liver plays an important role in the metabolism of xenobiotics and the metabolic reactions are mediated by many different kinds of enzymes. These enzymes mediate the detoxification in most cases, but are sometimes responsible for the bioactivation of xenobiotics. In this chapter, the pharm...

Hepatocellular Transport Systems: Basolateral Membrane

The basolateral membrane of hepatocytes is equipped with efficient transport systems for uptake of bile salts (Ntcp/NTCP) and xenobiotics (Oatps/OATPs). Under physiological conditions these transporters are important for ongoing bile formation and for efficient hepatic detoxification. Especial...

Hepatocyte Transplantation and Liver-Directed Gene Therapy

The research on liver-directed gene therapy and hepatocyte transplantation has progressed in parallel. Hepatocytes, with or without genetic modification have been used to introduce normal genes into patients or animal models with inherited disorders, while gene transfer can be used to expand h...

Mating Cell-Cell Channels in Conjugating Bacteria

Elisabeth Grohmann

Conjugative plasmid transfer is the most important mechanism for bacteria to deliver and acquire genetic information to cope with rapidly changing environmental conditions. To transfer genetic information intercellularly mating cell-cell channels between donor and recipient bacteria have to be e...

Mechanisms of Bile Formation—An Introduction

The formation of bile is a unique and vital function of the liver. Failure to form bile results in progressive cholestatic liver injury and death. Knowledge of the mechanism of bile formation has progressed rapidly in the past decade and this introduction provides a background and historical p...

Medical Therapy of Cholestatic Liver Diseases

Cholestasis and its sequelae are the hallmark of chronic cholestatic liver diseases and can be a feature of virtually all liver diseases at some point. Ursodeoxycholic acid (UDCA), a dihydroxy bile acid, is the only drug approved for the treatment of patients with primary biliary cirrhosis (PB...

Molecular Basis of Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) can be defined by the triad of positive PBC-specific autoantibodies (antimitochondrial antibodies (AMA) in >95%), cholestatic liver function tests and diagnostic or compatible liver histology. PBC is generally considered to be an autoimmune disease. To be accept...

Molecular Properties of Voltage-Gated Calcium Channels

errance P. Snutch, Jean Peloquin, Eleanor Mathews and John E. McRory Native Voltage-Gated Ca Channels

Early electrophysiological recordings from neurons, muscle and endocrine cells revealed voltage-activated calcium (Ca2+) currents with distinct characteristics, suggesting the existence of two major classes of Ca2+ channels based upon the membrane potentials at which they first open (see chapter ...

Molecular Transfers through Transient Lymphoid Cell-Cell Channels

Mary Poupot, Julie Gertner and Jean-Jacques Fournié

Intercellular communication is inherent to life, and has evolved with extremely diversified forms from prokaryotes to the most sophisticated multicellular eukaryotes. Haematopoietic cells from mammalians have adapted a transient and highly versatile means for the direct transfer of molecular i...

Monitoring Intracellular Ca2+ in Brain Slices with Fluorescent Indicators

Sean J. Mulligan and Brian A. MacVicar

Imaging fluorescent chemical indicators specific for calcium (Ca2+) has provided important insights into our current understanding of the many Ca2+ regulated cellular processes in the brain such as neurotransmitter release and synaptic plasticity. In this chapter we discuss the use of fluorescent...

Paracellular Pores in Endothelial Barriers

Luca Manzi and Gianfranco Bazzoni

The endothelium is an efficient barrier located at the boundary between vascular and perivascular compartments. However, it is also regarded to as a permeable filter that contains aqueous pores and allows selective passage of solutes between these compartments. Two distinct routes of permeabilit...

Pathology of Cholestasis

C formation may give rise to extensive parenchymal changes, without significant alterations in biliary tree morphology. Sepsis or systemic inflammatory conditions also can cause severe hepatocellular cholestasis without obstruction, although there may be attendant inflammatory changes in portal t...

Pathophysiological Basis of Pruritus and Fatigue in Cholestasis

Fatigue and pruritus are subjective complaints which are extremely common amongst patients with cholestasis, significantly impairing the quality of life of these patients. The genesis of these complaints appears to be complex and likely multi-factorial. Moreover, the central nervous syst...

Phosphatase Regulation of CFTR

John W. Hanrahan, Tang Zhu and L. Daniel Howell

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is tightly regulated by the opposing actions of protein kinases and phosphatases. Its phosphorylation and activation by protein kinases A (PKA) and C (PKC) have been studied in some detail but phosphatase regulation of t...