The role of cAMP and Ca on the modulation of junctional conductance: An integrated hypothesis

: The role of cAMP and Ca in the modulation of junctional permeability is discussed. An integrated hypothesis is presented which proposes that cAMP modulates the junctional conductance through the activation of specific kinases and phosphorylation of gap junction proteins. A close-loop feed-back between cAMP and Ca is assumed to be relevant in the regulation of junctional conductance under physiological conditions. According to this hypothesis hormones modulate the junctional permeability through variations in the intracellular concentration of cAMP. It is known that in several tissues the cells are connected through low resistance intercellular junctions (Loewenstein, 1966; Bennett, 1973; De Mello, 1975, 1932a). Ions and small molecules can flow freely from cell-to-cell across narrow hydrophilic channels (De Mello, 1982a). This type of intercellular coupling is essential for the fast propagation of the impulse and the synchronization of electrical activity in excitable tissues (Bennett, 1973; De Mello, 1982a). It has been proposed that the exchange of chemical signals between cells is important for metabolic cooperation (Gilula et al. 1972) and growth control (Loewenstein, 1979). Therefore, the modulation of junctional conductance is a significant feature of cell biology. Evidence has been provided that the increase in free [Ca2+]i can produce cell decoupling in Chironomus salivary gland (Loewenstein et al., 1967) and in mammalian cardiac fibers (De Mello, 1972, 1975). The free [Ca2+]i required to suppress cell-to-cell coupling is difficult to determine because Ca ions are continuously taken up by mitochondria, sarcoplasmic reticulum or are extruded from the cell. In salivary gland a concentration of free [Ca2+]i of about 5-8 X 10(-5) M was found to be associated with cell decoupling (Loewenstein et al., 1967). The major difficulty here is that the concentration of the ion determined in the bulk of the cytosol is not necessarily the same near the gap junctions.(ABSTRACT TRUNCATED AT 250 WORDS)