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In The Name of Allah Gap Junction Amirkabir University of Technology Biomedical Eng Department By: Mohammad Ali Ahmadi Pajouh March 2008 • Non Synaptic Cell-Cell Junctions: – Intermediate Junction – Desmosome – Gap Junction: • Local circuit current • Depolarization of the adjacent resting cell • 20 Angstrom in diameter • Molecules < 1000 daltons (750 daltons=1 angstrom= 1.0E-10 meter) Low Resistance – Resistance: • • • • Ca+ pH Electric Fields Sodium concentration • Electrical coupling via gap junctions is extremely important in the brain and for functioning of the heart (myocardium). Connexin-43 (Cx43) knock-out mice die early from heart misformations. Cell-cell channel connectivity is crucial for normal hearing, and mutations in Cx26 course non-syndromic deafness. • In nonexcitable cells, such as liver or lens cells, gap junctions mediated an exchange of metabolites which is vitally important, and mutations in Cx46 and Cx50 have been shown to be responsible for congenital cataracts. Charcot-Marie-Tooth disease is linked to mutations in Cx32 gene, which is expressed in liver and oligodendrocytes. Cardiac cells • Colatsky and Tsien: Electrical continuity of neighboring cardiac cells: Results • Behaves like a single uniform cell • Time constant=18 msec • Total intercellular resistivity =350 ohm cm = Low Intercellular Resistance Chapman and Fry: • ventricular trabeculea from frog ventricle • 6 different axial positions • Results: – Lambda= 0.328 – Thaw=4.15 msec – Total intercellular resistivity =588 ohm cm – Cytoplasmic Resistivity = 282 ohm cm – Remaining = 306 ohm cm • Cell: – Length 131 micrometer – Radius 7.5 micrometer • So, Lumped junctional resistance per cell = 2.2 M ohms • So, Specific junctional resistance = 4 ohm cm^2 • BUT resting membrane resistance= 2500 ohm cm^2 (*2 for two cells) • Results: – Cardiac intracellular space is electrically interconnected. – Activation in one part of tissue continuous contiguously to all surrounding tissue. Newer Data • Patch Clamp • Enzymatic technique for isolating cardiac cells Imaging of intracellular transport of Connexin43-GFP. Connexin-43 travels from the ER through the Golgi and is targeted to the plasma membrane at cell-cell interfaces where it forms gap junction channels • These gap junction subunits are transported anterogradely from the ER to the plasma membrane (PM) and stabilized there to form cell-cell channels. • Billion of neurons are connected with each other with exclusive specificity to develop a brain. • Electrical synapses important for the generation of synchronous oscillations are thought to be mediated by neuronal gap junctions.