| Modulation of Transmitter Release by Presynaptic Resting Potential and Background Calcium Levels Neuron, Volume 48, Issue 1, 6 October 2005, Pages 109-121 Gautam B. Awatramani, Gareth D. Price and Laurence O. Trussell Summary Activation of presynaptic ion channels alters the membrane potential of nerve terminals, leading to changes in transmitter release. To study the relationship between resting potential and exocytosis, we combined pre- and postsynaptic electrophysiological recordings with presynaptic Ca measurements at the calyx of Held. Depolarization of the membrane potential to between −60 mV and −65 mV elicited P/Q-type Ca currents of < 1 pA and increased intraterminal Ca by < 100 nM. These small Ca elevations were sufficient to enhance the probability of transmitter release up to 2-fold, with no effect on the readily releasable pool of vesicles. Moreover, the effects of mild depolarization on release had slow kinetics and were abolished by 1 mM intraterminal EGTA, suggesting that Ca acted through a high-affinity binding site. Together, these studies suggest that control of resting potential is a powerful means for regulating synaptic function at mammalian synapses. Summary | Full Text | PDF (471 kb) |
| The Role of Mitochondria in Presynaptic Calcium Handling at a Ribbon Synapse Neuron, Volume 25, Issue 1, 1 January 2000, Pages 229-237 David Zenisek and Gary Matthews Summary Mitochondria are thought to be important in clearing calcium from synaptic terminals. It is unclear, however, whether the principal role of mitochondria in presynaptic calcium handling is to take up Ca directly or to fuel Ca removal by other mechanisms. We used patch clamp techniques and fluorescence imaging to examine calcium clearance mechanisms, including mitochondrial uptake, in single synaptic terminals of retinal bipolar neurons. We found that extrusion through the ATP-dependent Ca pump of the plasma membrane is the dominant form of Ca removal in the synaptic terminal. Calcium uptake into mitochondria was sometimes evident with large Ca loads but was consistently observed only when plasma membrane extrusion was inhibited. We conclude that mitochondria act primarily as an energy source in clearance of Ca from bipolar cell synaptic terminals. Summary | Full Text | PDF (210 kb) |
| Compartmentalization of Calcium Extrusion Mechanisms in the Outer and Inner Segments of Photoreceptors Neuron, Volume 21, Issue 1, 1 July 1998, Pages 249-256 David Krizaj and David R Copenhagen Summary Differential localization of calcium channel subtypes in divergent regions of individual neurons strongly suggests that calcium signaling and regulation could be compartmentalized. Region-specific expression of calcium extrusion transporters would serve also to partition calcium regulation within single cells. Little is known about selective localization of the calcium extrusion transporters, nor has compartmentalized calcium regulation within single neurons been studied in detail. Sensory neurons provide an experimentally tractable preparation to investigate this functional compartmentalization. We studied calcium regulation in the outer segment (OS) and inner segment/synaptic terminal (IS/ST) regions of rods and cones. We report these areas can function as separate compartments. Moreover, ionic, pharmacological, and immunolocalization results show that a Ca-ATPase, but not the Na/K, Ca exchanger found in the OSs, extrudes calcium from the IS/ST region. The compartmentalization of calcium regulation in the photoreceptor outer and inner segments implies that transduction and synaptic signaling can be independently controlled. Similar separation of calcium-dependent functions is likely to apply in many types of neuron. Summary | Full Text | PDF (180 kb) |
Copyright © 1997 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 72, Issue 3, 1458-1471, 1 March 1997
doi:10.1016/S0006-3495(97)78792-7
Research Article
F. Helmchen, J.G. Borst and B. Sakmann
Abteilung Zellphysiologie, Max-Planck-Institut für medizinische Forschung, Heidelberg, Germany.
Calcium dynamics associated with a single action potential were studied quantitatively in the calyx of Held, a large presynaptic terminal in the rat brainstem. Terminals were loaded with different concentrations of high- or low-affinity Ca2+ indicators via patch pipettes. Spatially averaged Ca2+ signals were measured fluorometrically and analyzed on the basis of a single compartment model. A single action potential led to a total Ca2+ influx of 0.8–1 pC. The accessible volume of the terminal was about 0.4 pl; thus the total calcium concentration increased by 10–13 microM. The Ca(2+)-binding ratio of the endogenous buffer was about 40, as estimated from the competition with Fura-2, indicating that 2.5% of the total calcium remained free. This is consistent with the peak increase in free calcium concentration of about 400 nM, which was measured directly with MagFura-2. The decay of the [Ca2+]i transients was fast, with time constants of 100 ms at 23 degrees C and 45 ms at 35 degrees C, indicating Ca2+ extrusion rates of 400 and 900 s-1, respectively. The combination of the relatively low endogenous Ca(2+)-binding ratio and the high rate of Ca2+ extrusion provides an efficient mechanism for rapidly removing the large Ca2+ load of the terminal evoked by an action potential.