Transcript Gap Junction - Amirkabir University of Technology

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:
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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.