Nerve-evoked transmitter release at the fast synapse is triggered mainly by N-type and P/Q-type calcium channels. During postnatal development, however, the contribution of N-type calcium channels to synaptic transmission is lost and replaced by P/Q-type calcium currents at many synapses including the calyx of Held (Iwasaki et al. 2000).
To address the functional outcome of this developmental switch, using α1A subunit-ablated homozygous mutant and their wild-type littermate (WT) mice (9-12 days old, humanely killed by decapitation under halothane anaesthesia), we compared N-type and P/Q-type presynaptic calcium currents (IpCa) both directly recorded from the calyx of Held nerve terminal visually identified in thin brainstem slices.
IpCa in mutant mice were attenuated by 86 % (n = 4) by v{special}-conotoxin GVIA, whereas IpCa in WT mice were attenuated by 87 % (n = 6) by v{special}-agatoxin IVA, suggesting that the main component of IpCa in WT and mutant mice is P/Q-type and N-type, respectively. In the current-voltage relationship, IpCa in mutant mice had a peak 5 mV more positive than that of WT mice. In neither mutant nor WT mice did IpCa show a steady-state inactivation (between -130 mV and -40 mV). Inactivation, however, was observed in association with activation in both mutant and WT mice. IpCa undergoes facilitation upon repetitive activation in 8- to 17-day-old rats (Cuttle et al. 1998), being mediated by neuronal calcium sensor-1 (Tsujimoto et al. 2002). This facilitation was clearly seen in IpCa in WT mice. However, IpCa in mutant mice showed no facilitation in either the paired-pulse or high frequency (100 Hz, 10s) protocols.
We conclude that the activity-dependent IpCa facilitation is a distinct function of P/Q-type calcium channels.
This work was supported by Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science and Technology.