Facilitation versus depression in cultured hippocampal neurons determined by targeting of Ca(2+) channel Ca(v)β(4) versus Ca(v)β(2) subunits to synaptic terminals

Ca(2+) channel β subunits determine the transport and physiological properties of high voltage–activated Ca(2+) channel complexes. Our analysis of the distribution of the Ca(v)β subunit family members in hippocampal neurons correlates their synaptic distribution with their involvement in transmitter release. We find that exogenously expressed Ca(v)β(4b) and Ca(v)β(2a) subunits distribute in clusters and localize to synapses, whereas Ca(v)β(1b) and Ca(v)β(3) are homogenously distributed. According to their localization, Ca(v)β(2a) and Ca(v)β(4b) subunits modulate the synaptic plasticity of autaptic hippocampal neurons (i.e., Ca(v)β(2a) induces depression, whereas Ca(v)β(4b) induces paired-pulse facilitation [PPF] followed by synaptic depression during longer stimuli trains). The induction of PPF by Ca(v)β(4b) correlates with a reduction in the release probability and cooperativity of the transmitter release. These results suggest that Ca(v)β subunits determine the gating properties of the presynaptic Ca(2+) channels within the presynaptic terminal in a subunit-specific manner and may be involved in organization of the Ca(2+) channel relative to the release machinery.