The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse.
Repetitive nerve firings cause short-term depression (STD) of release at many synapses. Its underlying mechanism is largely attributed to depletion of a readily releasable vesicle pool (RRP) and a decreased probability of releasing a readily releasable vesicle during an action potential. Which of these two mechanisms is dominant and the mechanism that decreases the release probability remain debated. Here, we report that a decreased release probability is caused by a calcium-induced inhibition of presynaptic calcium channels, particularly P/Q-type channels at the calyx of Held in rat brainstem. This mechanism was the dominant cause of STD in a wide range of stimulation conditions, such as during 2 to 20 action potential-equivalent stimuli (AP-e) at 0.2-30 Hz and after 2 to 20 AP-e at 0.2-100 Hz. Only during > or = 100 Hz AP-e was depletion the dominant mechanism.
Xu
Jianhua
J
National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
Wu
Ling-Gang
LG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology; D050882:CREB-Binding Protein; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D002614:Chelating Agents / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D025802:Electric Capacitance; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008954:Models, Biological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009687:Nuclear Proteins / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors; D015534:Trans-Activators / Q000494:pharmacology
D015220:Calcium Channels; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009687:Nuclear Proteins; D010455:Peptides; D015534:Trans-Activators; C065738:MLCK peptide; D001464:Barium; C031938:calmidazolium; D004533:Egtazic Acid; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium