What mechanisms could account for agrin-mediated developmental switch from electrical to chemical synapses?
The more striking and unexpected effect of agrin reported here was its rapid and persistent inhibitory effect on gap junction mediated communication between neonate chromaffin cells. As evidenced by the continuous monitoring of Ij amplitude, agrin rapidly reduced electrotonic coupling (within a few minutes). Injection of LY up to several hours after agrin treatment revealed a persistent reduced dye spreading, thus indicating an agrin-mediated long-lasting effect. The blocking effect of the tyrosine kinase inhibitor PP2 on agrin-induced decreased gap junctional communication further indicates that Src family tyrosine kinases are involved in agrin-stimulated intracellular signaling pathway, as shown at the NMJ (Mittaud et al., 2001; Mohamed et al., 2001). Our result is consistent with the abundant expression of Src family kinases in neural tissue (Ross et al., 1988) from which chromaffin cells originated. Compelling evidence argues that connexin function can be regulated by activated tyr
