Abstract
AMPA-type glutamate receptor (AMPA-R) is recycling rapidly at the parallel fiber synapse in cerebellar Purkinje cell (PC). Blocking of constitutive exocytosis of AMPA-R by intracellular application of tetanus toxin (TeTx) reveals constitutive endocytosis of AMPA-R, which is independent of AMPA-R activity. Constitutive endocytosis of AMPA-R does not require elevation of intracellular Ca2+ concentration, and it is suppressed by concomitant inhibition of protein kinase C (PKC) and MAP kinase (ERK1/2). The maximum suppression level of PF-EPSC by TeTx is similar to that of botulinum toxin C1 (BoTx C). Thus, toxin resistant pool of AMPA-R is suggested to be a stable pool of the synaptic AMPA-R. LTD is induced even at the maximum reduction of PF-EPSC by TeTx, suggesting that LTD involves the process of destabilization of AMPA-R. Here, we examined the effects of actin-polymerization on constitutive and activity-dependent AMPAR trafficking. Actually, jasplakinolide, a blocker of actin-depolymerization, suppress both constitutive and activity dependent endocytosis of AMPA-R. Since toxin B inhibits also AMPA-R trafficking, mediation through Rho/Rac/Cdc42 is demonstrated in actin cytoskeleton regulation relating to AMPA-R trafficking. Immunocytochemical analysis shows that jasplakinolide suppress internalization of GluR2 in cultured PC. Thus, involvement of actin cytoskeleton is suggested in both constitutive and activity dependent AMPA-R trafficking at PF-synapse in cerebellar PC. [J Physiol Sci. 2007;57 Suppl:S84]
