TY - JOUR
T1 - "Fast" plasma membrane calcium pump PMCA2a concentrates in GABAergic terminals in the adult rat brain
AU - Burette, Alain C.
AU - Strehler, Emanuel E.
AU - Weinberg, Richard J.
PY - 2009/2/1
Y1 - 2009/2/1
N2 - The plasma membrane Ca2+-ATPases, (PMCA) represent the major high-affinity Ca2+ extrusion system in the brain. PMCAs comprise four isoforms and over 20 splice variants. Their different functional properties may permit different PMCA splice variants to accommodate different kinds of loCal [Ca2+] transients, but for a specific PMCA to play a Unique role in local Ca2+ handling it must be targeted to the appropriate-subcellular compartment. We used immunohistochemistry to study the spatial distribution of PMCA2a-one of the two major carboxyl-terminal splice variants of PMCA2-in the adult rat brain, testing whether this isoform, with especially high basal activity, is targeted to specific subcellular compartments. In striking contrast to the wide-spread distribution of PMCA2 as a whole, we found that PMCA2a is largely restricted to parvalbumin-positive inhibitory presynaptic terminals throughout the brain. The only major exception to this targeting pattern was in the cerebellar cortex, where PMCA2a also concentrates postsynaptically, in the spines of Purkinje cells. We propose that the fast Ca2+ activation kinetics and high Vmax of PMCA2a make this pump especially suited for rapid clearance of presynaptic Ca2+ in fast-spiking inhibitory nerve terminals, which face severe transient calcium loads.
AB - The plasma membrane Ca2+-ATPases, (PMCA) represent the major high-affinity Ca2+ extrusion system in the brain. PMCAs comprise four isoforms and over 20 splice variants. Their different functional properties may permit different PMCA splice variants to accommodate different kinds of loCal [Ca2+] transients, but for a specific PMCA to play a Unique role in local Ca2+ handling it must be targeted to the appropriate-subcellular compartment. We used immunohistochemistry to study the spatial distribution of PMCA2a-one of the two major carboxyl-terminal splice variants of PMCA2-in the adult rat brain, testing whether this isoform, with especially high basal activity, is targeted to specific subcellular compartments. In striking contrast to the wide-spread distribution of PMCA2 as a whole, we found that PMCA2a is largely restricted to parvalbumin-positive inhibitory presynaptic terminals throughout the brain. The only major exception to this targeting pattern was in the cerebellar cortex, where PMCA2a also concentrates postsynaptically, in the spines of Purkinje cells. We propose that the fast Ca2+ activation kinetics and high Vmax of PMCA2a make this pump especially suited for rapid clearance of presynaptic Ca2+ in fast-spiking inhibitory nerve terminals, which face severe transient calcium loads.
KW - Calcium extrusion
KW - Calcium pump
KW - Fast-spiking basket cells
KW - Immunohistochemistry
KW - Parvalbumin
KW - Presynaptic terminals
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U2 - 10.1002/cne.21909
DO - 10.1002/cne.21909
M3 - Article
C2 - 19025983
AN - SCOPUS:59649114442
SN - 0021-9967
VL - 512
SP - 500
EP - 513
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 4
ER -