Ca²⁺-Dependent, Stimulus-Specific Modulation of the Plasma Membrane Ca²⁺Pump in Hippocampal Neurons

Abstract

Ferragamo MJ, Reinardy JL, Thayer SA. Ca 2ϩ -dependent, stimulus-specific modulation of the plasma membrane Ca 2ϩ pump in hippocampal neurons.

Reduced expression of the Ca2+transporter protein PMCA2 slows Ca2+dynamics in mouse cerebellar Purkinje neurones and alters the precision of motor coordination

“…Working in this way, the consequences of reduced PMCA2 activity would be a reduced calcium buffer capacity (since in its absence calcium would stay bound to parvalbumin and calbindin for longer), raised resting calcium levels and a slowing of both phases of the calcium recovery, all consistent with our findings. Furthermore, since PMCA2 is an active and modifiable enzymatic mechanism its ability to fine‐tune calcium levels in a close relationship with the buffers could also influence calcium signalling dynamics under different physiological conditions (Ferragamo et al 2009).…”

Molecular interactions of the plasma membrane calcium ATPase 2 at pre- and post-synaptic sites in rat cerebellum

“…The high level of colocalisation between PSD95 and PMCA2 and NR2a and PMCA2 in the cerebellar granule cell layer where fully functional calcium permeable NMDA receptors (containing NR1 and NR2a subunits) drive the plasticity of the mossy fibre to granule cell pathway (D'Angelo et al ., 1999), supports the idea that the partnership functions during sustained depolarisation and NMDA receptor activation. More recently, in hippocampal pyramidal neurones, where PMCA2b is also expressed, NMDA receptor mediated calcium entry was shown to slow the extrusion kinetics of the PMCA (Scheuss et al , 2006) through a protease mediated mechanism (Ferragamo et al , 2009). This provides supporting evidence for a close partnership between the NMDA receptor and PMCA2b.…”

Calcium Signaling in Dendritic Spines

“…The efficacy of PMCA is itself regulated by intracellular Ca 2þ such that at high Ca 2þ concentrations, the efficiency of PMCA-dependent Ca 2þ extrusion is decreased, resulting in slowed Ca 2þ clearance during prolonged excitation (Scheuss et al 2006). The mechanism of this slowing may include Ca 2þ -dependent activation of proteases that act on PMCA (Ferragamo et al 2009), although this irreversible mechanism cannot account for the transient slowing of Ca 2þ clearance seen following action potential trains (Scheuss et al 2006). The proteins comprising the Na þ /Ca 2þ exchangers (NCX1-3) have also been localized to dendrites and dendritic spines with the distribution varying by isoform (Lorincz et al 2007;Minelli et al 2007).…”