Developmental changes in calcium channel types mediating central synaptic transmission

Multiple types of high-voltage-activated Ca2+ channels trigger neurotransmitter release at the mammalian central synapse. Among them, the omega-conotoxin GVIA-sensitive N-type channels and the omega-Aga-IVA-sensitive P/Q-type channels mediate fast synaptic transmission. However, at most central synapses, it is not known whether the contributions of different Ca2+ channel types to synaptic transmission remain stable throughout postnatal development. We have addressed this question by testing type-specific Ca2+ channel blockers at developing central synapses. Our results indicate that N-type channels contribute to thalamic and cerebellar IPSCs only transiently during early postnatal period and P/Q-type channels predominantly mediate mature synaptic transmission, as we reported previously at the brainstem auditory synapse formed by the calyx of Held. In fact, Ca2+ currents directly recorded from the auditory calyceal presynaptic terminal were identified as N-, P/Q-, and R-types at postnatal day 7 (P7) to P10 but became predominantly P/Q-type at P13. In contrast to thalamic and cerebellar IPSCs and brainstem auditory EPSCs, N- type Ca2+ channels persistently contribute to cerebral cortical EPSCs and spinal IPSCs throughout postnatal months. Thus, in adult animals, synaptic transmission is predominantly mediated by P/Q-type channels at a subset of synapses and mediated synergistically by multiple types of Ca2+ channels at other synapses.