Function and Physiology of Gap Junction Channels

Gap junctional channels, like many other ion channels, can be modulated via second messengers and via phosphorylation processes. Besides these, intracellular calcium and pH have been proven to be important regulators of channel function. In this chapter the short-term regulatory processes are considered, i.e. processes on a time scale of minutes. Besides this, regulatory processes are known which take place over a period of 30 min up to several hours and which involve formation or synthesis of new gap junction channels. The latter processes are described in the following chapter. 

Gap junction conductance (gj) of neonatal rat heart cells varies with temperature (37 °C, 48.3 nS 14 °C, 21.4 nS -2°C, 17.5 nS) [Bukauskas and Weingart, 1993] so that gj has been assumed to be at least in part enzymatically controlled. Several protein kinases are known to be involved in the regulation of the gap junction channels. However, the situation is rather complicated since the same protein kinase may enhance or reduce gap junctional conductance in different tissues or in different species. Thus, generalizations should be avoided and the specific condition has to be taken into account. One of the first to be described was protein kinase A (PKA), the cAMP-dependent protein kinase, which can enhance junctional conductance in hepatocytes coupled via Cx32 and Cx26 [Saez et al., 1986, 1990]. Similarly, an increase in junctional conduc- 

In horizontal cells of turtle and fish retinae, a dopamine-induced increase in intracellular cAMP levels is associated with cellular uncoupling [DeVries and Schwartz, 1989 McMahon et al., 1989] (the connexin isoform involved is not identified). Inhibition of phosphodiesterase with IBMX after stimulation of adenylate cyclase using forskolin resulted in an increase in intracellular 

Protein kinase Connexin Tissue Permeability g. Reference 

0=No effect permeability = as assessed by dye coupling gj = assessed by measurement of electrical  

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