Calmodulin-dependent inactivation of presynaptic calcium currents and its contribution to synaptic depression at developing calyceal synapses

Abstract

At calyces of Held of immature rats, Ca²⁺- and calmodulin (CaM)-dependent inactivation of presynaptic Ca²⁺ currents (I_pCa) is proposed to underlie synaptic depression. At postnatal day (P) 7-9, I_pCa evoked by a 1-ms depolarizing pulse showed a prominent paired-pulse inactivation of Ca²⁺ currents (PIC) at 0.1-2 s inter-stimulus intervals, and CaM inhibitors attenuated PIC and short-term synaptic depression as reported. However, at P13-15, PIC became very small and CaM inhibitors no longer affected PIC or synaptic depression. In contrast, at P13-15, a CaM inhibitor still attenuated I_pCa inactivation during a long pulse (2 s) depolarization, to a similar extent as at P7-9. Consistently, CaM immuno-reactivity at P15 calyces was indistinguishable from that at P7. These results suggest that the residual intra-terminal Ca²⁺ concentration following a brief depolarizing pulse or an action potential is insufficient for CaM to inactivate I_pCa at P13-15. Whole-cell dialysis of P13-15 calyces with a pipette solution containing no Ca²⁺ buffer had no effect on PIC, whereas loading 10-mM EGTA into P7-8 calyces blocked PIC. We conclude that spatial segregation of Ca²⁺ channels in the nerve terminal, rather than an increase in endogenous Ca²⁺ buffer proteins, may underlie the developmental decline of CaM-dependent I_pCa inactivation. [J Physiol Sci. 2007;57 Suppl:S83]