Gap junction channel regulation

Moreno AP, Saez JC, Fishman GI, Spray DC Human connexin 43 gap junction channels. Regulation of unitary conductances by phosporylation. Circ Res 1994b 74 1050-1057. 

In some cases such variability has consequences for the regulation of the gap junction channels. Thus, in rat Cx32 the serine residue at position 233 is... 

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-... 

The cGMP-dependent PKG is also involved in the regulation of gap junction channels. Activation of PKG by cGMP or cGMP analogues, such... 

Fig. 13. Synopsis of the physiological regulators of gap junction channels. = PKC changes the substate of conductance, =not found by all investigators as differences between the various isoforms of connexins or species variabilities. 

Rook et al., 1988] that the regulation of gap junction conductance is not the all or nothing and not quantal, but graduate so that different single-channel conductances or substates have been postulated [Page, 1991]. This is probably reflected by various substates of single-channel conductance found in various gap junctional channels which will be discussed as well. 

Kwak BR, Hermanns MMP, De Jonge HR, Lohmann SM, Jongsma HJ, Chanson M Differential regulation of distinct types of gap junction channels by similar phosphorylating conditions. Mol Biol Cell 1995a 6 1707-1719. 

Kwak BR, Jongsma HJ Regulation of cardiac gap junction channel permeability and conductance by several phosphorylating conditions. Mol Cell Biochem 1996 157 93-99. 

Peracchia C Possible involvement of caffeine and ryanodine-sensitive calcium stores in low pH-induced regulation of gap junction channels in Peracchia C (ed) Biophysics of Gap Junction Channels. Boca Raton, CRC Press, 1991a, pp 13-28. 

Spray, D.C. (1994) Physiological and pharmacological regulation of gap junction channels. Molecular Mechanisms of Epithelial Cell Junctions From Development to Disease. Editors. Chi 195-215. RG Landes, Austin... 

John, G. R., Scemes, E., Suadicani, S. O., Liu, J. S., Charles, P. C., Lee, S. C., Spray, D. C., and Brosnan, C. F. (1999). IL-lbeta differentially regulates calcium wave propagation between primary human fetal astrocytes via pathways involving P2 receptors and gap junction channels. Proc. Natl. Acad. Sci. USA 96, 11613-11618. 

Gap junction channels provide pathways for direct current flow between cells and for regulated intercellular movement of important cellular signaling molecules, including cyclic nucleotides (5, 13-17). Consequently, gap junction channels are thought to play crucial regulatory roles in cell biology, development,and physiology (18-22). 

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