Gap junction function

The immunohistochemical findings were correlated with reduced intercellular coupling indicating a possible role of disturbed Cx43 expression and gap junction function in the pathogenesis of Chagas disease and the arrhythmias associated with that disease. 

Synapses are electrical or chemical communicative contacts between neurons. Electrical synapses (neuronal gap junctions) function by the propagation of electrical impulses from one cell to another (and vice versa) via direct, physical contact. As a consequence, these synapses are characterized by a relatively simple organization of membrane structure and associated organelles (Zoidl et al. 2002). Electrical synapses are also less mutable, in terms of their function and molecular characteristics, and thus exhibit little of the plasticity that typifies the chemical synapse. 

Figure 5 Cellular/tissue functions linked to gap junction function.

Epigenetic Toxicity as a Resuit of inappropriate Moduiation of Gap Junction Function... 

Figure 6 Disease states correlated with defective gap junction function.

Figure 8 Use of the scrape loading/dye transfer assay to screen for agents that can prevent inhibition of gap junction function.

Classical approaches to verification of functional gap junctions include conductance measurement, pharmacological manipulation, and demonstration of dye coupling (28). Dye coupling is a straightforward method for demonstrating gap junctional function. Injection experiments are simple and results are easily interpreted. The outcome is assessed immediately with an in vivo preparation. A lower dye concentration is necessary for detection because dye lost during fixation and tissue processing is avoided. 

Hu, J., Speisky, H., Cotgreave, I. A. (1995). The inhibitory effects of boldine, glaucine, and probucol on TPA -induced down regulation of gap junction function relationships to intracellular peroxides, protein kinase C translocation, and cotmexin 43 phosphorylation. Biochem. Pharmacol, 50(10), 1635-1643. 

It has been hypothesized that the mechanisms whereby mefloquine increases the risk of seizures in patients with a history of seizures, which may be via altered neuronal calcium homeostasis, altered gap-junction functioning, and neuronal cell death, are particularly associated with a mutation in EPMl, a gene that is associated with progressive myoclonic epilepsy type 1, and hence altered GABA activity [10 ]. The author proposed that mefloquine should be contraindicated in people with the EPMl mutation and in those with a history of myoclonus or ataxia, or a family history of degenerative neurological disorders that are consistent with the presence of the EPMl mutation. 

In the Unites States, the daily intake of 3-carotene is around 2 mg/day Several epidemiological studies have reported that consumption of carotenoid-rich foods is associated with reduced risks of certain chronic diseases such as cancers, cardiovascular disease, and age-related macular degeneration. These preventive effects of carotenoids may be related to their major function as vitamin A precursors and/or their actions as antioxidants, modulators of the immune response, and inducers of gap-junction communications. Not all carotenoids exert similar protective effects against specific diseases. By reason of the potential use of carotenoids as natural food colorants and/or for their health-promoting effects, research has focused on better understanding how they are absorbed by and metabolized in the human body. 

Action potentials are generated in single-unit smooth muscle. Simultaneous depolarization of 30 to 40 smooth muscle cells is required to generate a propagated action potential the presence of gap junctions allows this to occur readily. Because single-unit smooth muscle is self-excitable and capable of generating action potentials without input from the autonomic nervous system, it is referred to as myogenic. In this muscle, the function of the autonomic nervous system is to modify contractile activity only. Input is not needed to elicit contraction. 

Gap junctions provide electrical communication between cells, forming a functional syncytium Myogenic... 

From the SA node, the heart beat spreads rapidly throughout both atria by way of the gap junctions. As mentioned previously, the atria are stimulated to contract simultaneously. An interatrial conduction pathway extends from the SA node to the left atrium. Its function is to facilitate conduction of the impulse through the left atrium, creating the atrial syncytium (see Figure 13.3). 

Unscheduled DNA synthesis was not induced in either mouse or hirman primary hepatocyte cultures with mono(2-ethylhexyl) phthalate, and neither this metabolite nor 2-ethylhexanol induced mutations in mouse lymphoma cells in vitro. Mono(2-ethyl-hexyl) phthalate induced sister-chromatid exchange in Chinese hamster V79 cells and chromosomal aberrations in Syrian hamster embryo cells. It also induced transformation in Syrian hamster embryo cells, but not in mouse C3H10T /2 cells. Gap-junctional intercellular communication was inhibited by mono(2-ethylhexyl) phthalate in Syrian hamster embryo cells and in Chinese hamster V79 cells. As reported in an abstract (Baker et al., 1996), this function was also inhibited in rat and mouse hepatocytes, but not in Syrian hamster or human hepatocytes. 

---