title: Spike-mediated and graded inhibitory synaptic transmission between leech interneurons: evidence for shared release sites.
abstract: Inhibitory synaptic transmission between leech heart interneurons consist of two components: graded, gated by Ca2+ entering by low-threshold [low-voltage-activated (LVA)] Ca channels and spike-mediated, gated by Ca2+ entering by high-threshold [high-voltage-activated (HVA)] Ca channels. Changes in presynaptic background Ca2+ produced by Ca2+ influx through LVA channels modulate spike-mediated transmission, suggesting LVA channels have access to release sites controlled by HVA channels. Here we explore whether spike-mediated and graded transmission can use the same release sites and thus how Ca2+ influx by HVA and LVA Ca channels might interact to evoke neurotransmitter release. We recorded pre- and postsynaptic currents from voltage-clamped heart interneurons bathed in 0 mM Na+/5 mM Ca2+ saline. Using different stimulating paradigms and inorganic Ca channel blockers, we show that strong graded synaptic transmission can occlude high-threshold/spike-mediated synaptic transmission when evoked simultaneously. Suppression of LVA Ca currents diminishes graded release and concomitantly increases the ability of Ca2+ entering by HVA channels to release transmitter. Uncaging of Ca chelator corroborates that graded release occludes spike-mediated transmission. Our results indicate that both graded and spike-mediated synaptic transmission depend on the same readily releasable pool of synaptic vesicles. Thus Ca2+, entering cells through different Ca channels (LVA and HVA), acts to gate release of the same synaptic vesicles. The data argue for a closer location of HVA Ca channels to release sites than LVA Ca channels. The results are summarized in a conceptual model of a heart interneuron release site.
authors.affiliation: Department of Biology, Emory University, Atlanta, GA 30322, USA. Andrei.Ivanov@emory.edu
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Ivanov
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Calabrese
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D003979:Diazonium Compounds / Q000494:pharmacology; D004594:Electrophysiology; D017952:Ganglia, Invertebrate / Q000502:physiology*; D006321:Heart / Q000294:innervation / Q000502:physiology; D047709:Hirudo medicinalis / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D009930:Organic Chemicals / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010642:Phenoxyacetates / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002614:Chelating Agents; D003979:Diazonium Compounds; D009930:Organic Chemicals; D010642:Phenoxyacetates; C063685:diazo-2; C071335:calcium orange; D012964:Sodium; D002118:Calcium