Presentation on theme: "Model of the epithelium and its principal compartments"— Presentation transcript:
1Model of the epithelium and its principal compartments Tight junctionApical membraneBasolateralmembraneBasement membraneTranscellular fluxParacellular fluxLIS - Lateral intercellular spaceTight junction
3Interaction of epithelial cells with basement membrane Principal proteins of the basement membraneEpithelial cell is attached to the basement membrane via integrins (heterodimer receptors)
4Transport of solutes across epithelium Ji Flux of transported molecule/ionst Staverman reflection coefficientCi Intraepithelial concentration of the solute iJV Volume flowPi Permeability coefficientDci Concentration difference mucosa-serosazi ValencyF Faraday numberDj Transepithelial voltage„solvent drag“electrodiffusionactive transportNaCl transport in renal proximal tubuleJiNa100 %29 %32 %38 %Cl49 %51 %0 %
5Transport of solutes active transport primary secondary Malpighian tubule (Insects)Frog skin, urinary bladder, colon, renal collecting tubule, etc.
6Conductance of epithelial cells Ion conductances of plasma membrane, membrane potencialsEffect of hypotonic stress on membrane conductanceBarium and DIDS sensitive conductance is induced by hypotonic stress
7Transport of solutes and water JV Volume flowLP Hydraulic conductivityDp Hydrostatic pressure differenceR Gas constantT Absolute temperatureDc1 Concentration difference mucosa-serosaDc2 Concentration difference mucosa-serosast Staverman reflection coefficient
8Equivalent electrical circuit for the epithelium Rap = parallel resistance (1/conductance) for individual ion species that move across the apical membraneEap = parallel electromotive forces equal to Nernst equilibrium potentials of individual ion species that move across the apical membraneRbl, Ebl = the same for the basolateral membraneEp = electromotive force of the electrogenic ion pump of the basolateral membrane (Na,K-ATPasa)Rts = resistance of the tight junctionEpc = electromotive force corresponding to the diffusion potential of the tight junctionRlis = resistance of the lateral intercellular space
9Mechanisms of NaCl (NaHCO3) absorption Transcellular NaCl transportTranscellular NaHCO3 transportTranscellular transport of Na+ and paracellular transport of Cl-Transcellular NaCl transport
10NaCl and water secretion Transcellular transport of Cl- via NKCC cotransporter on the basolateral membrane and chloride channel CFTR on the apical membrane. The negative charges that move across the cell from the interstitium to lumen generate a lumen-negative voltage that can drive passive Na+ secretion across the paracellular pathway (tight junctions). The driving force is the secondary active transport of Cl- across the basolateral membrane.CFTR
12Acid-base transport – luminal alkalinization Exchangers
13Potassium transportTranscellular secretion: K+ is taken up by Na-K pump across the basolateral membrane to be secreted across the apical membrane via potassium channels.Paracellular absorption trough tight junctions.Transcellular primarily active absorption driven by H-K-pump.
14Control of epithelial transport Cell control – „crosstalk“ between apical and basolateral membrane – protection against the increasing concentration of osmolytes in the cytoplasmTissue control – e.g.. enteric nervous system,Organism control – e.g. hormones calcitriol, aldosterone, vasopressinHormone regulatory pathways – endocrine, paracrine, autocrine, intracrineNervous regulatory pathways – symphatetic, parasymphatetic and enteric nervous systemsImmune regulatory pathways – mucosal immune system