Modulation of transmitter release by presynaptic resting potential and background calcium levels.
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.
Awatramani
Gautam B
GB
Oregon Hearing Research Center/Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
Price
Gareth D
GD
Trussell
Laurence O
LO
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
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