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.
Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
R
R
Etcheberrigaray
J L
JL
Fiedler
H B
HB
Pollard
E
E
Rojas
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