title: Presynaptic plasma membrane Ca2+ ATPase isoform 2a regulates excitatory synaptic transmission in rat hippocampal CA3.
abstract: 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 submicromolar 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 colocalized with the presynaptic marker proteins synaptophysin and the vesicular glutamate transporter 1, but not with the postsynaptic density protein PSD-95. PMCA2a also did not colocalize with glutamic acid decarboxylase-65, a marker of GABA-ergic terminals, although it did localize 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 presynaptic excitatory terminals regulated excitatory synaptic transmission within hippocampal CA3.
authors.affiliation: School of Biological Sciences, Royal Holloway University of London, UK.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Jensen
authors.forename: Adelaida G
authors.initials: AG
authors.lastname: Filoteo
authors.forename: Thomas
authors.initials: T
authors.lastname: Knopfel
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Empson
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D007536:Isomerism; D009433:Neural Inhibition / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D017729:Presynaptic Terminals / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D053499:Plasma Membrane Calcium-Transporting ATPases