Regulation of presynaptic calcium in a mammalian synaptic terminal

Abstract

Ca2+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 Ca2+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 Ca2+under conditions of high Ca2+load, maintaining intraterminal Ca2+near resting levels. Indeed, the effect of the mitochondria was so powerful that the ability to clamp intraterminal Ca2+with a somatically positioned whole cell patch pipette was compromised. The plasma membrane Ca2+-ATPase (PMCA), but not the Na+/Ca2+exchanger (NCX) or the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), was an important regulator of resting Ca2+. Furthermore, PMCA activity, but not NCX or SERCA activity, was essential for the recovery of Ca2+levels following depolarization-evoked Ca2+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 Ca2+at rest and after a stimulus-evoked Ca2+rise, the PMCA is poised to modulate luminance coding and adaptation to background illumination in the mammalian rod bipolar cell.