Plasma membrane calcium ATPase isoforms (PMCAs) are expressed in a wide variety of tissues where cell-specific expression provides ample opportunity for functional diversity amongst these transporters. The PMCAs use energy derived from ATP to extrude sub-micromolar concentrations of intracellular Ca²⁺ ([Ca²⁺]i) out of the cell. Their high affinity for Ca²⁺ and the speed with which they remove [Ca²⁺]i depends upon splicing at their carboxy (c) -terminal site. Here we provide biochemical and functional evidence that a brain-specific, C-terminal truncated and therefore fast variant of PMCA2, PMCA2a, has a role at hippocampal CA3 synapses. PMCA2a was enriched in forebrain synaptosomes and in hippocampal CA3 it co-localised with the pre-synaptic marker proteins synaptophysin and the vesicular glutamate transporter 1, VGLUT1, but not with the post-synaptic density protein PSD-95. PMCA2a also did not co-localise with glutamic acid decarboxylase-65, GAD-65, a marker of GABA-ergic terminals, although it did localise to a small extent with parvalbumin-positive presumed inhibitory terminals. Pharmacological inhibition of PMCA increased the frequency but not the amplitude of mEPSCs with little effect on mIPSCs or paired pulse depression of evoked IPSCs. However, inhibition of PMCA activity did enhance the amplitude and slowed the recovery of paired pulse facilitation (PPF) of evoked EPSCs. These results indicated that fast PMCA2a mediated clearance of [Ca²⁺]i from pre-synaptic excitatory terminals regulated excitatory synaptic transmission within hippocampal CA3.