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L14 The Paracellular Pathway2011

L14 The Paracellular Pathway2011 - COPYRIGHT Mammalian...

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1/ 13 COPYRIGHT Prof. Beyenbach Mammalian Physiology, BIOAP 4580 Spring 2011 THE PARACELLULAR PATHWAY 1) Points of cell contact. As cells come together and form tissues, they seal their unity by way of three major structures: desmosomes, gap junctions, and tight junctions (Fig. 1). Fig. 1. Design of epithelia. The transcellular pathway is defined as the pathway through epithelial cells (two membranes in series with an intermediate cytoplasmic compartment). The paracellular pathway is defined as the transport route between epithelial cells through tight (or septate) junctions and around gap junctions and desmosomes. Gap junctions offer an intracellular pathway (tunnel) between adjacent epithelial cells for the lateral diffusion of, for example, second messengers. Desmosomes are "spot welds" that give structural support for epithelial sheets and tubes. a) Desmosomes. Desmosomes (zona adherence) are points of cell adhesion that provide structural adhesion. They are like welding spots between cells. They prevent the tearing of tissue for some eternity as in leather (Fig. 1). b) Gap junctions. Gap junctions are tunnel-like structures between neighboring cells. They couple cells electrically, forming a functional syncytium as in the myocardium (heart). Gap junctions eliminate the need for synaptic transmission as an action potential passes from one cell to the next uninterrupted along a „continuous‟ cell membrane. Intercellular "tunnels" also allow the lateral transport of intracellular second messengers from cell to cell (Fig. 1). In the case of injury to one cell, gap junctions to neighboring cells close which uncouples cells. Uncoupling is dependent on the presence of Ca 2+ in the extracellular medium. In Ca 2+ free media the cells may dissociate but not close their gap junctions. As a result, neighboring cells will "leak" their contents through open gap
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2/ 13 junctions to the extracellular medium and die. Gap junctions resemble membrane channels in that they conduct ions and currents. Cells coupled by gap junctions share the same membrane voltage, at rest and during action potentials. An action potential sweeping quickly across millions of myocardial cells in the heart causes them to contract in unison, summing their single individual contractions to generate the collective force of the myocardium that evacuates the ventricular volume into the aorta (and pulmonary artery). In addition to electrical continuity, gap junctions also allow the passage of large molecules, cAMP and other intracellular second messengers. c) Tight junctions. Tight junctions (zona occludence) are found in epithelial cells but also in endothelial cells. They are glycoprotein structures near the apical membrane of epi- and endothelial cells (Fig. 1). They hold epithelial cells together akin to the plastic ring of a six-pack of Coca Cola. Next to providing structural support, tight junctions play a critical role in transepithelial transport. When tight junctions are "tight", the epithelium
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L14 The Paracellular Pathway2011 - COPYRIGHT Mammalian...

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