TY - JOUR
T1 - Membrane depolarization evokes neurotransmitter release in the absence of calcium entry
AU - Hochner, B.
AU - Parnas, H.
AU - Parnas, I.
PY - 1989
Y1 - 1989
N2 - The discovery that Ca2+ is necessary for the release of neurotransmitter, the primary means by which nerve cells communicate, led to the calcium hypothesis of neutransmitter release1-4, in which release is initiated after an action potential only by an increase in intracellular Ca2+ concentration near the release sites and is terminated (1-2 ms) by the rapid removal of Ca2+. Since then, the calcium-voltage hypothesis has been proposed5,6, in which the depolarization of the presynaptic terminals has two functions. First, in common with the calcium hypothesis, the Ca2+ conductance is increased, thereby permitting Ca2+ entry. Second, a confor-mational change is induced in a membrane molecule that renders it sensitive to Ca2+, and then binding of Ca2+ to this active form triggers release of neurotransmitter. When the membrane is repolarized, the molecule is inactivated and release is terminated, regardless of the local Ca2+ concentration at that moment. This hypothesis, in contrast to the calcium hypothesis, accounts for the insensitivity of the time course of release to experimental manipulations of intracellular Ca2+ concentation7-11, Furthermore, it explains rapid termination of release after depolarization, even though Ca2+ concentration may still be high. Here we describe experiments that distinguish between these two hypotheses and find that our results support the calcium voltage hypothesis.
AB - The discovery that Ca2+ is necessary for the release of neurotransmitter, the primary means by which nerve cells communicate, led to the calcium hypothesis of neutransmitter release1-4, in which release is initiated after an action potential only by an increase in intracellular Ca2+ concentration near the release sites and is terminated (1-2 ms) by the rapid removal of Ca2+. Since then, the calcium-voltage hypothesis has been proposed5,6, in which the depolarization of the presynaptic terminals has two functions. First, in common with the calcium hypothesis, the Ca2+ conductance is increased, thereby permitting Ca2+ entry. Second, a confor-mational change is induced in a membrane molecule that renders it sensitive to Ca2+, and then binding of Ca2+ to this active form triggers release of neurotransmitter. When the membrane is repolarized, the molecule is inactivated and release is terminated, regardless of the local Ca2+ concentration at that moment. This hypothesis, in contrast to the calcium hypothesis, accounts for the insensitivity of the time course of release to experimental manipulations of intracellular Ca2+ concentation7-11, Furthermore, it explains rapid termination of release after depolarization, even though Ca2+ concentration may still be high. Here we describe experiments that distinguish between these two hypotheses and find that our results support the calcium voltage hypothesis.
UR - http://www.scopus.com/inward/record.url?scp=0024421377&partnerID=8YFLogxK
U2 - 10.1038/342433a0
DO - 10.1038/342433a0
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C2 - 2573839
AN - SCOPUS:0024421377
SN - 0028-0836
VL - 342
SP - 433
EP - 435
JO - Nature
JF - Nature
IS - 6248
ER -