title: Modulation of transmitter release by presynaptic resting potential and background calcium levels.
abstract: 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(2+) measurements at the calyx of Held. Depolarization of the membrane potential to between -60 mV and -65 mV elicited P/Q-type Ca(2+) currents of < 1 pA and increased intraterminal Ca(2+) by < 100 nM. These small Ca(2+) 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(2+) 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.
authors.affiliation: Oregon Hearing Research Center/Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Gautam B
authors.initials: GB
authors.lastname: Awatramani
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Price
authors.forename: Laurence O
authors.initials: LO
authors.lastname: Trussell
mesh_terms: D060848:Agatoxins; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology*; D019256:Cadmium Chloride / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016257:Fura-2 / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D060848:Agatoxins; D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D018377:Neurotransmitter Agents; D013111:Spider Venoms; C060465:omega-agatoxin I; D013779:Tetrodotoxin; D004533:Egtazic Acid; D009532:Nickel; D019256:Cadmium Chloride; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D016257:Fura-2