Presentation on theme: "Model of the epithelium and its principal compartments"— Presentation transcript:
1 Model of the epithelium and its principal compartments Tight junctionApical membraneBasolateralmembraneBasement membraneTranscellular fluxParacellular fluxLIS - Lateral intercellular spaceTight junction
3 Interaction of epithelial cells with basement membrane Principal proteins of the basement membraneEpithelial cell is attached to the basement membrane via integrins (heterodimer receptors)
4 Transport 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 %
5 Transport of solutes active transport primary secondary Malpighian tubule (Insects)Frog skin, urinary bladder, colon, renal collecting tubule, etc.
6 Conductance 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
7 Transport 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
8 Equivalent 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
9 Mechanisms of NaCl (NaHCO3) absorption Transcellular NaCl transportTranscellular NaHCO3 transportTranscellular transport of Na+ and paracellular transport of Cl-Transcellular NaCl transport
10 NaCl 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
12 Acid-base transport – luminal alkalinization Exchangers
13 Potassium 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.
14 Control 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