Endoplasmic reticulum as a source of Ca2+ in neurotransmitter secretion.
Depolarization of the synaptosomal membrane by a rapid elevation of [K+]0 induces secretion of adenosine-5'-triphosphate (ATP) as well as the specific neurotransmitters. In addition to the classical [Ca2+]0-dependent mode, we have found that ATP secretion also occurred in the absence of extracellular calcium [( Ca2+]0 less than 1 microM). The extent of both modalities of secretion depended on membrane potential, and the [Ca2+]0-independent secretion proceeded at a rate that was substantially smaller than that of the [Ca2+]0-dependent mode at all membrane potentials examined. We propose that intracellular stores may provide the Ca2+ required for exocytosis in the [Ca2+]0-independent mode of ATP secretion. To test this hypothesis, we searched for the presence of Ca(2+)-release channels gated by intracellular messengers in our synaptosomal preparation. We fused membrane vesicles from lysed synaptosomes with acidic phospholipid bilayers formed at the tip of a patch pipette and found that these membranes contained a Ca(2+)-selective channel. The properties of this channel resemble those of the Ca(2+)-release channel reconstituted from sarcoplasmic reticulum membrane vesicles. These include size of the single open-channel conductance (75 pS Cs+ as the main current carrier), activation by adenine nucleotides (ATP), ryanodine and caffeine, and inhibition by ruthenium red.
Etcheberrigaray
R
R
Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Fiedler
J L
JL
Pollard
H B
HB
Rojas
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D002118:Calcium