Regulation of presynaptic calcium in a mammalian synaptic terminal.

Ca(2+) signaling in synaptic terminals plays a critical role in neurotransmitter release and short-term synaptic plasticity. In the present study, we examined the role of synaptic Ca(2+) handling mechanisms in the synaptic terminals of mammalian rod bipolar cells, neurons that play a pivotal role in the high-sensitivity vision pathway. We found that mitochondria sequester Ca(2+) under conditions of high Ca(2+) load, maintaining intraterminal Ca(2+) near resting levels. Indeed, the effect of the mitochondria was so powerful that the ability to clamp intraterminal Ca(2+) with a somatically positioned whole cell patch pipette was compromised. The plasma membrane Ca(2+)-ATPase (PMCA), but not the Na(+)/Ca(2+) exchanger (NCX) or the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), was an important regulator of resting Ca(2+). Furthermore, PMCA activity, but not NCX or SERCA activity, was essential for the recovery of Ca(2+) levels following depolarization-evoked Ca(2+) entry. Loss of PMCA function was also associated with impaired restoration of membrane surface area following depolarization-evoked exocytosis. Given its roles in the regulation of intraterminal Ca(2+) at rest and after a stimulus-evoked Ca(2+) rise, the PMCA is poised to modulate luminance coding and adaptation to background illumination in the mammalian rod bipolar cell.