CA2- A BIDIRECTIONAL, RECEPTOR-ORIENTED FORM OF CA2+ SIGNALING( WAVESIN PC12 NEURITES )

Spatial and temporal aspects of Ca2+ signaling were investigated in PC 12 cells differentiated with nerve growth factor, the well known nerve cell model. Activation of receptors coupled to polyphosphoinositide h ydrolysis gave rise in a high proportion of the cells to Ca2+ waves pr opagating non decrementally and at constant speed (2-4 mu m/s at 18 de grees C and similar to 10-fold faster at 37 degrees C) along the neuri tes. These waves relied entirely on the release of Ca2+ from intracell ular stores since they could be generated even when the cells were inc ubated in Ca2+-free medium. In contrast, when the cells were depolariz ed with high K+ in Ca2+-containing medium, increases of cytosolic Ca2 occurred in the neurites but failed to evolve into waves. Depending o n the receptor agonist employed (bradykinin and carbachol versus ATP) the orientation of the waves could be opposite, from the neurite tip t o the cell body or vice versa, suggesting different and specific distr ibution of the responsible surface receptors. Cytosolic Ca2+ imaging r esults, together with studies of inositol 1,4,5-trisphosphate generati on in intact cells and inositol 1,4,5-trisphosphate-induced Ca2+ relea se from microsomes, revealed the sustaining process of the waves to be discharge of Ca2+ from the inositol 1,4,5-trisphosphate- (and not the ryanodine) sensitive stores distributed along the neurites. The activ ation of the cognate receptor appears to result from the coordinate ac tion of the second messenger and Ca2+. Because of their properties and orientation, the waves could participate in the control of not only c onventional cell activities, but also excitability and differential pr ocessing of inputs, and thus of electrochemical computation in nerve c ells.