Effects of staurosporine on exocytosis and endocytosis at frog motor nerve terminals.
Observations of the dynamic staining and destaining of FM1-43 in frog motor nerve terminals (Henkel and Betz, 1995) suggested that staurosporine might shorten the interval between exocytosis and endocytosis, inducing a "kiss and run" mode of exocytosis and endocytosis. We tested this hypothesis by using FM1-43 imaging (to measure the time course of FM1-43 endocytosis), intracellular recording of evoked synaptic potentials (to measure acetylcholine release), and electron microscopy (to examine synaptic vesicle distribution). Staurosporine reduced FM1-43 uptake during but not after a tetanus, increased the speed of end plate potential (EPP) amplitude rundown, and greatly slowed the recovery from synaptic depression. Ultrastructural observations showed pronounced vesicle depletion near active zones after tetanic stimulation in staurosporine-treated preparations. These results suggest that staurosporine acted primarily to impair mobilization of synaptic vesicles during tetanic stimulation.
Becherer
U
U
Department of Physiology and Biophysics, University of Colorado Medical School, Denver, Colorado 80262, USA. ubecher@gwdg.de
Guatimosim
C
C
Betz
W
W
D000818:Animals; D004558:Electric Stimulation; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects* / Q000502:physiology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D011894:Rana pipiens; D019311:Staurosporine / Q000494:pharmacology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
C073804:FM1 43; D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D019311:Staurosporine