William J. Betz, Ph.D.
Professor and Chairman
Department of Physiology & Biophysics
UCD at Fitzsimons
RC-1 North Tower, P18-7129. PO Box 6511, Mail Stop F8307. Tel (303)
724-4502. Fax (303) 724-4501.
Email bill.betz@UCHSC.edu.
Bill's Curriculum vitae
Matlab programs
Bill is a
program member.
CURRENT RESEARCH
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FM1-43. We have developed and characterized fluorescent dyes that stain the
membranes of recycled synaptic vesicles. The best dye is FM1-43, which was synthesized by Dr. Fei
Mao of Molecular Probes, Inc. Three properties make FM dyes useful for studying exocytosis, endocytosis,
and endosomal trafficking: (1) the dyes partition reversibly in membranes; (2) the dyes do not 'flip
flop' and so are never free in the cytoplasm; (3) the dyes are far more fluorescent in membranes than in
water.
 Frog motor nerve terminals (2-3 um in diameter) stain in a punctate fashion. Each
spot is a cluster of several hundred stained synaptic vesicles. During repetitive stimulation, they
destain in a few minutes. The experiment illustrated in this time-lapse movie lasted 3.5 minutes; the
nerve was stimulated repetitively at 30 Hz.(If the movie stops, press 'Reload'.)
Combined imaging with FM1-43 (to label synaptic vesicles) and Fura-2 (to monitor
intracellular calcium ion concentration) is possible.
Blue=low [Ca++]i; red=high [Ca++]i  Bovine
adrenal chromaffin cells also stain with FM1-43 in an activity-dependent fashion. Since
they can also be patch clamped, simultaneous measurements of membrane capacitance can be made with these
cells, permitting independent monitoring of exocytosis and endocytosis. The picture shows five confocal
images taken by Dr. Corey Smith before, during, and after stimulation in the presence of FM1-43. In the 5
images here, FM1-43 was present in the bathing solution during all but the last image (the medium is not
fluorescent because FM dyes are not fluorescent in water). The first two images were obtained 5 minutes
apart (no change means no spontaneous exocytosis). Then nicotine (0.01 mM) was added to the bathing
solution; images 3 and 4 were obtained 15 seconds and 5 minutes after nicotine. The last image was
obtained 20 minutes after washing nicotine and FM1-43 from the bath (note how the surface destained). Rat anterior
pituitary lactotrophs exhibit discrete bright spots when stimulated (movie 1). Evidently the dense cores
of lactotrophs, unlike those of chromaffin cells (above) contain hydrophobic domains that stain with FM
dyes. Each spot reflects the exocytosis of a single secretory granule. The spots persist indefinitely,
and are eventually endocytosed (movie 2). Treatment with dopamine, which reduced cyclic AMP, causes the
spots to dissolve and disappear (movie 3), although on the bottom of the cell, the spots are trapped
against the coverslip and do not disappear (movie 4).
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We are currently working on several projects. Silvio Rizzoli is
examining pathways of FM dye uptake and recycling in  motor nerve terminals.
In collaboration with Professor Robert Zorec (Ljubljiana) we are using digital deconvolution microscopy and capacitance monitoring to examine exocytosis in  pituitary lactotrophs. We were introduced to the study of rat anterior pituitary
cells by Itzhak Nussinovitch (Hebrew University, Jerusalem). The lactotrophs are especially
interesting because they show individual bright spots that may mark single exocytic sites.
Dot Dill provides us with expert help in electron microscopy, and the assistance of Steve Fadul is invaluable in just about all aspects of every project.    Recent colleagues |
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Click here to see the mother of all exocytic events
REPRESENTATIVE PUBLICATIONS
 Betz, W.J., F.
Mao & G.S. Bewick. (1992). Activity- dependent staining and destaining of living vertebrate motor nerve
terminals. J. Neurosci. 12: 363-375. (cover illustration) |
 Betz, W.J. &
G.S. Bewick. (1992). Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction.
Science 255: 200-203. (cover illustration) |
| Betz, W.J. & G.S. Bewick. (1993). Optical and electrophysiological
monitoring of transmitter release and synaptic vesicle recycling at the frog neuromuscular junction.
J. Physiol. 460, 287-309. |  Betz, W.J. and
A. Henkel. (1994). Okadaic acid disrupts clusters of synaptic vesicles in frog motor nerve terminals.
J. Cell Biol., 124, 843-854. (cover illustration) |
| Henkel, A., J. Lübke and W.J. Betz. (1996). FM1-43 ultrastructural
localization in and release from frog motor nerve terminals. Proc. Natl. Acad. Sci. USA, 93,
1918-1923. | Smith, C.B. and Betz, W.J. (1996). Simultaneous independent measurement of endo- and exocytosis. Nature, 380, 531-534. |
| Betz, W.J., Mao, F., and Smith, C.B. (1996). Imaging exocytosis and endocytosis. Curr. Opinion in Neurobiol. 6, 365-371. | Henkel, A.W., L. Simpson, R.M.A.P. Ridge and W.J. Betz. (1996). Synaptic
vesicle mobilization monitored by fluorescence photobleach recovery in living nerve terminals stained
with FM1-43. J. Neurosci. 16, 3960-3967. |
| Wu, L.-G. and Betz, W.J. (1996). Nerve activity but not intracellular calcium determines the time course of endocytosis at the frog neuromuscular junction. Neuron, 17, 769-779. | 
Angleson, J.K. and Betz, W.J. (1997). Monitoring secretion in real time: capacitance, amperometry, and
fluorescence compared. Trends in Neurosci, 20, 281-286 (with poster)
To see poster,click on picture |
| Betz, W.J. and Angleson, J.K. (1997). Cell secretion: Now you see it, now you don't. [News and Views] Nature, 388, 423-424. | Wu, L.-G. and W.J. Betz (1998) Kinetics of synaptic depression and vesicle recycling after tetanic stimulation of frog motor nerve terminals. Biophys. J., 74: 3003-3009. |
| Angleson, J.K. and Betz, W.J. (1998). The synaptic vesicle cycle. Ann. Rev. Physiol., 60: 347-363. pdf | Cochilla, A.J., J.K. Angleson and W.J. Betz (1999). Monitoring secretory membrane with FM1-43 fluorescence. Ann. Rev. Neurosci., 22, 1-10. |
| Angleson, J.K., Cochilla, A.J., Kilic, G., Nussinovitch, I., and Betz, W.J. (1999) Regulation of dense core release from neuroendocrine cells revealed by imaging single exocytic events. Nature Neurosci., 2, 440-446 | Wu, L.-G. and Betz, W.J. (1999) Spatial variability in release at the frog neuromuscular junction measured with FM1-43. Can. J. Physiol. Pharmacol. 77, 672-678 |
| Betz, W.J. and Richards, D.A. (2000) What goes out must come in [News and Views]. Nature Neurosci., 3, 636-637. | Cochilla, A.J., Angleson, J.K., and Betz, W.J. (2000) Differential regulation of granuel-to-granule and granule-to-plasma membrane fusion during secretion from rat pituitary lactotrophs. J. Cell Biol., 150, 829-848. |
| Richards, D.A., Guatimosim, C., and Betz, W.J. (2000) Two endocytic recycling routes fill two vesicle pools in frog motor nerve terminals. Neuron, 27, 551-559. | Kilic, G., Angleson, J.K., Cochilla, A.J., Nussinovitch, I., and Betz, W.J. (2001). Sustained stimulation of exocytosis triggers continuous membrane retrieval in rat pituitary somatotrophs. J. Physiol., 532, 771-83. |
| Angleson J.K., and Betz W.J. (2001). Intraterminal Ca(2+) and spontaneous transmitter release at the frog neuromuscular junction. J Neurophysiol. 85, 287-294. | Becherer U., Guatimosim C., and Betz W.J. (2001) Effects of staurosporine on exocytosis and endocytosis at frog motor nerve terminals. J Neurosci. 21, 782-787. |
| Rizzoli, S.O. and Betz, W.J. (2002). Effects of 2-(4-Morpholinyl)-8-Phenyl-4H-1-Benzopyran-4-One on Synaptic Vesicle Cycling at the Frog Neuromuscular Junction. J. Neurosci. 2002 22: 10680-10689. | Rizzoli, S.O. and Betz, W.J. (2003). All change at the synapse. Nature 423, 591-592. [News and Views] |
| Richards, D.A., Guatimosim, C., Rizzoli, S.O., and Betz, W.J. (2003). Synaptic vesicle pools at the frog neuromuscular junction. Neuron 39, 529-541. | Rizzoli, S.O., Richards, D.A., and Betz, W.J. (2003) Monitoring synaptic vesicle recycling in frog motor nerve terminals with FM dyes. J. Neurocytol. 32, 539-549. pdf |
| Richards, D.A., Rizzoli, S.O. and Betz, W.J. (2004) Effects of wortmannin and latrunculin A on slow endocytosis at the frog neuromuscular junction. J. Physiol. 557, 77-91. pdf | Rizzoli, S.O. and Betz, W.J. (2004) The structural organization of the readily releaseable pool of synaptic vesicles. Science. 203, 2037-2039. pdf |
| S.O. Rizzoli, S.O., Becherer, U., Angleson, J., and Betz, W.J. (2005) Imaging synaptic vesicle dynamics with styryl dyes, in Imaging in Neuroscience and Development, Cold Spring Harbor Laboratory Press, pp. 475-486. |  Rizzoli, S.O. and Betz, W.J.
(2005) Synaptic Vesicle Pools. Nature Rev. Neurosci.. 6, 57-70. (cover illustration) pdf |
| Gaffield, M.A., Rizzoli, S.O., and Betz, W.J. (2006). Mobility of synaptic vesicles in different pools in resting and stimulated frog motor nerve terminals. Neuron, 51, 317-325. pdf |
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