Ribbon synapses of vertebrate photoreceptors constantly release glutam
ate in darkness, Transmitter release is maintained by a steady influx
of calcium through voltage-dependent calcium channels, implying the pr
esence of a mechanism that is able to extrude calcium at an equal rate
. The two predominant mechanisms of intracellular calcium extrusion ar
e the plasma membrane calcium ATPase (PMCA) and the Na+/Ca2+-exchanger
. Immunohistochemical staining of retina sections revealed strong immu
noreactivity for the PMCA in rod and cone terminals, whereas staining
for the Na+/Ca2+-exchanger was very weak, The PMCA was localized to th
e plasma membrane along the sides of the photoreceptor terminals and w
as excluded from the base of the terminals where the active zones are
located. The amplitude of a calcium-activated chloride current was use
d to monitor the intracellular calcium concentration. An upper limit f
or the time required to remove intracellular free calcium is obtained
from two time constants measured for the calcium-activated chloride cu
rrent tail currents: one of 50 msec and a second of 190 msec, Calcium
extrusion was inhibited in the absence of intracellular ATP or in the
presence of the PMCA inhibitor orthovanadate, but was unaffected by re
placement of external Na+ with Li+. The data indicate that the PMCA, r
ather than the Na+/Ca2+-exchanger, is the predominant mechanism for ca
lcium extrusion from photoreceptor synaptic terminals.