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exceed 1 mM in bipolar-cell synaptic term-

Synaptic vesicle inals, even with moderate stimulation. So
releasable vesicles would be exhausted rapid-
ly if the exocytosis machinery here were as
Synaptotagmin sensitive as that at the calyx of Held. Perhaps
Synaptobrevin low Ca2& affinity is a hallmark of sustained
neurotransmitter release, whereas the brev-
Ca2+ Ca2+ Ca2+ ity of Ca2& signals driven by action potentials
Ca2+
Ca2+ Ca2+ allows for higher Ca2& affinity and greater
Vesicle Ca2+
Inside membrane integration of local Ca2& signals.
It is almost 50 years since Katz and col-
Plasma
membrane } leagues embarked on the work that still
forms the cornerstone of our understanding
Outside
Ca2+ channel Ca2+ channel of how neurons talk to each other8. But this
Ca2+ Syntaxin SNAP-25 Ca2+ field is as exciting as ever, and it is thrilling to
be able to watch single vesicles as they fuse, to
Figure 2 Kinetics of calcium-dependent neurotransmitter release. This close-up view of a nerve observe directly the stages before exocytosis,
terminal shows a synaptic vesicle docked at the plasma membrane near two Ca2& channels. During and to begin to glimpse the calcium signals
priming, the plasma-membrane proteins syntaxin and SNAP-25 and the vesicle protein that trigger fusion. ■
synaptobrevin form a complex required for vesicle fusion with the plasma membrane9. The Ca2& Gary Matthews is in the Department of
sensor that triggers fusion is thought to be the vesicle protein synaptotagmin9. Schneggenburger and Neurobiology and Behavior, State University of New
Neher2 and Bollmann et al.3 show that the Ca2& concentration needed to trigger fusion is lower than York, Stony Brook, New York 11794-5230, USA.
previously thought. So the Ca2& sensor does not need to be close to a single Ca2& channel, where the e-mail: Gary.G.Matthews@sunysb.edu
Ca2& concentration is very high. Instead it can be some distance away from the channels, where the 1. Zenisek, D., Steyer, J. A. & Almers, W. Nature 406, 849–854
Ca2& concentration is lower as a result of diffusion. This means that more than one Ca2& channel can (2000).
2. Schneggenburger, R. & Neher, E. Nature 406, 889–893 (2000).
influence neurotransmitter release. (Modified from ref. 10.)
3. Bollmann, J. H., Sakmann, B. & Borst, J. G. G. Science 289,
953–956 (2000).
Meanwhile, Schneggenburger and Neher2 These results2,3 differ significantly from 4. Steyer, J. A., Horstmann, H. & Almers, W. Nature 388, 474–478
and Bollmann et al.3 have been looking at those of similar experiments on retinal (1997).
5. Steyer, J. A. & Almers, W. Biophys. J. 76, 2262–2271 (2000).
the way in which vesicle fusion depends on bipolar neurons7, where increases in Ca2& 6. Neher, E. Neuron 20, 389–399 (1998).
calcium. Averaged across the whole terminal, concentration to 10–100 mM were needed to 7. Heidelberger, R., Heinemann, C., Neher, E. & Matthews, G.
the concentration of Ca2& inside the neuron drive exocytosis. But unlike neurons in the Nature 371, 513–515 (1994).
rises from about 0.1 mM to just under 0.5 mM calyx of Held, bipolar neurons release neuro- 8. Katz, B. The Release of Neural Transmitter Substances (Liverpool
Univ. Press, Liverpool, 1969).
during neuronal stimulation. But vesicle transmitters over relatively long periods and 9. Südhof, T. C. Nature 375, 645–653 (1995).
fusion is thought to be triggered by the much do not fire action potentials, which tend to be 10. Matthews, G. Neurobiology: Molecules, Cells and Systems 2nd
higher Ca2& concentrations (more than brief. The global Ca2& concentration can edn (Blackwell, Malden, MA, in the press).
100 mM) near the open mouth of individual
Ca2& channels6 (Fig. 2). It now appears2,3 that
such high concentrations are not needed. Chemistry
Schneggenburger and Neher2 and Bollmann
et al.3 released ‘caged’ Ca2& to produce known
levels of Ca2& in the calyx of Held — a large Another noble gas conquered
synaptic terminal that allows nerve impulses Gernot Frenking
in both the signalling and the receiving
neurons to be recorded simultaneously. The
authors found that a rise in Ca2& concentra-

tion in the signalling neuron to 10 mM or less
was enough to drive fast neurotransmitter
release. They estimate that an action poten-
tial (the electrical change in a neuron that
follows stimulation) activates the exocytosis
of synaptic vesicles by raising Ca2& levels to
10–25 mM for about 0.5 ms.
Apparently, it is not important for the
exocytosis machinery and Ca2& channels to
be near each other to allow rapid neurotrans-
mitter release (Fig. 2) — Ca2& can diffuse
some distance away from a channel into the
cell, its concentration declining as it diffuses,
and still trigger neurotransmitter release.
This means that single vesicles might be
influenced by Ca2& ions entering through
several channels. If so, and if the Ca2& sensor
is therefore not saturated by concentrated
Ca2& influx through a single open channel,
greater control of neurotransmitter release
becomes possible.
836
O
n page 874 of this issue Khriachtchev et
al.1 report the synthesis of the first
compound containing the noble gas
argon. This leaves only two stable elements in
the periodic table — helium and neon — for
which no neutral compound exists. But the
experimental strategy that was successful for
argon might also work for these elements.
One of the most fundamental questions
in chemistry, which remained unanswered
for a long time, was what drives the chemical
elements to form stable molecules. Why are
some elements very reactive, some less reac-
tive, and a peculiar small group of elements,
known as noble gases, not reactive at all?
Quantum theory finally explained these
observations by showing that the electrons
within atoms are arranged in shells around
the atomic nucleus. Each shell can only take a
fixed number of electrons, and a completely
filled shell is energetically very favourable. So
the driving force behind chemical reactions
© 2000 Macmillan Magazines Ltd
H
133
Ar
197
F
Figure 1 Argon is no longer alone. The first
neutral argon molecule, synthesized by
Khriachtchev et al.,1 is HArF, a stable hydride
compound. The numbers give the calculated
distances between the atoms in picometres.
is the filling of electron shells by release or
uptake of electrons, or by sharing electrons
with neighbouring atoms, which leads to the
formation of chemical bonds.
The noble gases have a completely filled
outer electron shell, so there is no driving
force for these elements to engage in chemi-
cal bonding, as the energetically most stable
arrangement of electrons already exists in
the neutral atoms. Many chemists believed
that it was impossible to synthesize a stable
molecule containing a noble gas element,
NATURE | VOL 406 | 24 AUGUST 2000 | www.nature.com

Astronomy
Lights go on all over Europe
BLACKWELL SCIENCE
Astronomers at last week’s
general assembly of the
International Astronomical
Union in Manchester expressed
concerns about rampant light
pollution. High-resolution
satellite images reveal the extent
of the problem (Cinzano, P. et al.
Mon. Not. R. Astron. Soc., in the
press). This map of Europe shows
the ratios between artificial and
natural sky brightness (red is
the worst at more than 9:1).
but others saw the reluctance of the elements
helium, neon, argon, krypton, xenon and
radioactive radon to form chemical bonds as
a great challenge to experimental chemistry.
They were supported in their quest by theo-
retical predictions made by the late Nobel
prizewinner Linus Pauling2, who predicted
in 1933 that molecules containing xenon and
krypton should exist.
It took nearly 30 years before Pauling’s
theory was verified by experiment. The
breakthrough came in 1962 when Neil
Bartlett found that the strongly oxidizing
agent platinum hexafluoride, PtF6, is power-
ful enough to ionize (that is, to remove an
electron from) an oxygen molecule, O2,
yielding the stable salt compound
(O2)&(PtF6)1. Bartlett recognized that the
energy needed to remove an electron from
xenon is slightly less than the ionization
energy of O2, so he carried out the same
experiment with xenon and PtF6. The spon-
taneous reaction produced the first neutral
compound to contain a noble gas3. Bartlett’s
discovery was soon followed by syntheses of
many other compounds of xenon, and also
of krypton, which has only a slightly higher
ionization energy than xenon4.
This suggests that the ionization energy
of the noble gases should be a measure of
their willingness to form a chemical bond.
The ionization energy, IE, is measured in
electron volts, eV. Xenon (IE = 12.13 eV)
compounds are indeed more stable than
krypton (IE = 14.00 eV) compounds.
Quantum chemical calculations predicted
that neutral compounds of argon (IE = 15.76
eV) should also exist, because its ionization
energy is still lower than that of fluorine
(IE = 17.42 eV). Therefore, salt compounds
of ArF& with suitable anions might be stable,
although synthesizing them would be a
formidable task5. Compounds of helium
(IE = 24.59 eV) and neon (IE = 21.56 eV)
were not expected to be stable because of
their very high ionization energies6.
Khriachtchev et al.1 have now synthesized
NATURE | VOL 406 | 24 AUGUST 2000 | www.nature.com
the first stable neutral argon compound,
HArF (Fig. 1). This is an important mile-
stone in the history of chemistry, because the
number of elements for which no neutral
molecule has been synthesized is now only
two. It is also an exciting accomplishment
because the strategy used by the authors was
different from the one suggested by theory.
HArF is not a salt compound. More exciting
is the fact that the type of noble-gas bonding
in HArF might also be found in the neon
compound HNeF, and even in the helium
compound HHeF. In fact, theoretical calcu-
lations announced last year predicted that
HHeF could be a stable neutral molecule7.
It should be noted that molecules such as
HArF are only kinetically stable and exist
only in a low-temperature solid matrix (in
this case made from inert argon). The mole-
cules rapidly decompose if they come into
contact with each other or if they are warmed
up, because they break up into unbound
argon atoms and HF, which are much more
stable species. It is only the energy barrier
involved in breaking the weak H–ArF bond
that prevents it from spontaneous decom-
position. So HArF does not fall into the same
category as the numerous xenon and kryp-
ton compounds, which can easily be pre-
pared and handled in solutions or as solid
salt compounds. Nonetheless, the work of
Khriachtchev et al. is a further breakthrough
in the field of noble-gas chemistry, and
might even help chemists to conquer the two
least reactive elements, neon and helium. ■
Gernot Frenking is at the Fachbereich Chemie,
Philipps-Universität Marburg, Hans-Meerwein-
Strasse, D-35039 Marburg, Germany.
e-mail: frenking@chemie.uni-marburg.de
1. Khriachtchev, L., Pettersson, M., Runeberg, N., Lundell, J. &
Räsänen, M. Nature 406, 874–876 (2000).
2. Pauling, L. J. Am. Chem. Soc. 55, 1895–1900 (1933).
3. Bartlett, N. Proc. Chem. Soc. 218 (1962).
4. Laszlo, P. & Schrobilgen, G. Angew. Chem. Int. Edn Engl. 27,
479–489 (1988).
5. Frenking, G., Koch, W., Deakyne, C. A., Liebman, J. & Bartlett,
N. J. Am. Chem. Soc. 111, 31–33 (1989).
6. Frenking, G. & Cremer, D. Structure Bonding 73, 17–95 (1990).
7. Wong, M. W. J. Am. Chem. Soc. 122, 6289–6290 (2000).
© 2000 Macmillan Magazines Ltd
news and views
100 YEARS AGO
An interesting and detailed account of Count
von Zeppelin’s successful trial trip of his
navigable balloon on July 2 is given in Die
Umschau by an anonymous author, who has
endeavoured to dispel the somewhat
exaggerated reports which have been
circulated as to the success or failure of the
experiment. It is pointed out that the delay in
the ascent, which some persons attributed
to an accident, was really caused by the
wind being too strong at the time originally
proposed for the trip. The wind-velocity at
the time of starting was 5.5 metres per
second, and the balloon was actually driven
forwards for a short time in the face of this
wind… The wind causing the balloon to drift
towards the shore, a descent was made in
order that Count Zeppelin might land on the
water (to use an Irishism), and thus have his
machine towed back by steamer. The
descent was very gradual, the cars gently
sinking down to the water without the
sudden jerk which is commonly experienced
in an ordinary balloon.
From Nature 23 August 1900.
50 YEARS AGO
If we slide one solid body over another, there
is a resistance to the motion which we call
friction. What is the cause of this, and what
is really happening at the interface between
the solids during sliding? It is usually
considered that friction is a nuisance, and
from the earliest times man has made
ingenious attempts to eliminate or to
diminish it to as small a value as possible.
It is not so much the work we have to do in
overcoming the friction—the power loss—
which is important, although this can be
considerable. In a modern motor-car, for
example, about 20 per cent of the power is
wasted in overcoming friction… The real
trouble is the damage that is done by the
friction—the wear or seizure of some vital
part of the machine. It is this factor, perhaps
more than any other, which limits the design
and which shortens the effective life of,
say, an aero-engine or other complex
machine. Nevertheless, the credit side is
considerable: if the coefficient of friction
were much less than it is, walking would
be impossible and we should have to use
cog wheels or perhaps some system of
suction pads like an octopus to get about at
all. Conversely, if it were much higher than
it is, we should just stick fast wherever we
were put.
From Nature 26 August 1950.
837