INHIBITION OF ENDOCYTOSIS BY ELEVATED INTERNAL CALCIUM IN A SYNAPTIC TERMINAL

DURING synaptic transmission in the nervous system, synaptic vesicles fuse with the plasma membrane of presynaptic terminals, releasing neur otransmitter by exocytosis(1,2). The vesicle membrane is then retrieve d by endocytosis and recycled into new transmitter-containing vesicles . Exocytosis in synaptic terminals is calcium-dependent(7-9), and we n ow report that endocytosis also is regulated by the intracellular calc ium concentration ([Ca2+](i)). Capacitance measurements(10,11) in syna ptic terminals of retinal bipolar neurons revealed that endocytosis wa s strongly inhibited by elevated [Ca2+](i) in the range achieved by Ca 2+-current activation. The rate of membrane retrieval was steeply depe ndent on [Ca2+](i), with a Hill coefficient of 4 and half-inhibition a t similar to 500 nM. At [Ca2+](i) greater than or equal to 900 nM, end ocytosis was entirely absent. The action of internal calcium on endocy tosis represents a novel negative-feedback mechanism controlling the r ate of membrane recovery in synaptic terminals after neurotransmitter secretion. As membrane retrieval is the first step in vesicle recyclin g, this mechanism may contribute to activity-dependent synaptic depres sion.