Gap-junction coupling

In contrast to cAMP, a stimulation of PKC with phorbol esters (TPA) has been shown to play an important role in the downregulation of gap junctional coupling [Yancey et al., 1982]. Since reestablishment of intercellular coupling was not seen after wash out of TPA in the presence of the protein synthesis inhibitor, puromycin [Fitzgerald et al., 1983], the phorbol ester probably induces the elimination of junctional channels under these conditions. Thus, it might be possible that PKC is involved in the regulation of channel degradation. 

In the following a survey is given of the substances which have been found to alter intercellular coupling. First drugs will be considered which uncouple gap junctions. A number of lipophilic compounds have been described to reduce gap junctional coupling. These substances include alcohols like hep-tanol and octanol, saturated and unsaturated fatty acids, and alcohols and... 

Fig. 23. Survey of the various pharmacological interventions at the gap junctional coupling. For details see text. 

For the problem of prophylactic antiarrhythmic treatment these antiarrhythmic peptides are probably not the final solution. Because of their peptide nature they are not well suited for in vivo studies and they are probably only indicated for the prevention of arrhythmias due to reduced coupling, but they are a first step in the direction of a new class of drugs influencing gap junctional coupling. 

The various pharmacological approaches to the modulation of gap junctional coupling are summarized in figure 23. 

Peters NS New insights into myocardial arrhythmogenesis Distribution of gap junctional coupling in normal, ischaemic and hypertrophied hearts. Clin Sci 1996 90 447-452. 

Somogyi R, Kolb HA Cell-to-cell channel conductance during loss of gap junctional coupling in pairs of pancreatic acinar and Chinese hamster ovary cells. Pflugers Arch 1988a 412 54—65. 

Champeil-Potokar G., Chaumontet C., Guesnet P., Lavialle M., and Denis I. (2006). Docosahexaenoic acid (22 6n-3) enrichment of membrane phospholipids increases gap junction coupling capacity in cultured astrocytes. Eur. J. Neurosci. 24 3084-3090. 

A. Sherman and). Rinzel Model for synchronization of pancreatic ft -cells by gap junction coupling. Biophys.J. 1991, 59 547-559. 

The implications of individual neuron dynamics on neuronal network synchronization is evident. In Fig. 7.9 (from Schneider et al., unpublished data) this is demonstrated with network simulations (10 x 10 neurons) of nearest neighbor gap-junction coupling. It is illustrated in quite a simple form which, in a similar way, can also be experimentally used with the local mean field potential (LFP). In the simulations LFP simply is the mean potential value of all neurons. In the nonsynchronized state LFP shows tiny, random fluctuations. In the completely in-phase synchronized states the spikes should peak out to their full height... 

Fig. 7.9 Computer simulations of a neuronal network (lOx 10 neurons) with nearest neighbor gap-junction coupling (see equations). The diagrams show the local mean field potentials (LFP) which are calculated as the mean potential values V of all neurons during continuously increasing coupling strength gc- Insets illustrate the different types of patterns in which the neurons originally operate (with randomly set initial values), (a) The network of tonic firing...

Fig. 7.10 Computer simulation of two gap-junction coupled neurons which originally are operating at different dynamic states, one in the tonic firing regime and the other one in the bursting regime (also indicated in Fig. 6.8b by the points T and B, respectively with the arrow S pointing on the completely synchronized state), (a) Bifurcation diagrams of interspike intervals (ISI) of the originally...

Osteocytes are formed by the incorporation of osteoblasts into bone matrix. They remain in contact with other osteocytes via gap junction-coupled cell processes that form small channels through the matrix, the canaliculi. These small channels connect the cell body containing lacunae with each other and ECM external to the bone and play an important role in mechano-chemical transduction. 

S. Weng, M. Lauven, T. Schaefer, L. Polontchouk, R. Grover, S. Dhein, Pharmacological modification of gap junction coupling by an antiarrhythmic peptide via protein kinase C activation, Faseb J16,1114-1116. 

Yoshizaki, G., R. Patino, P. Thomas, D. Bolamba and X. Chang. Effects of maturation-inducing hormone on heterologous gap junctional coupling in ovarian follicles of Atlantic croaker. Gen. Comp. Endocrinol. 124 359-366, 2001. 

Kohling, R, Gladwell, SJ, Biacd, E, Vteugdenhil, M, Jefferys, JG (2001) Prolonged epileptiform bursting induced by 0-Mg(2 + ) in rat hippocampal slices depends on gap junctional coupling. Neuroscience, 105 579-587. 

Although cadherins do not exclusively cluster, the formation of adherens junctions is important for several tissue functions [18]. In epithelial tissues cadherins mediate zonula adherens junctions, which partition the cell membrane into apical and basolateral surfaces. In neuronal cells they mechanically stabilize synaptic junctions by mediating adhesion between the presynaptic and postsynaptic cells. In cardiac myocytes they establish intercalated discs, which both stabilize gap junctional coupling and transmit contractile forces. 

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