Graded inhibitory synaptic transmission between leech interneurons: assessing the roles of two kinetically distinct
Andrei I Ivanov1, Ronald L Calabrese
1Department of Biology, Emory University, Atlanta, GA 30322, USA. Andrei.Ivanov@emory.edu
Insights
Calcium channels in leech heart interneurons differentially control synaptic transmission. Rapidly activating calcium currents (ICaF) are more effective than slowly activating currents (ICaS) for graded transmission, impacting heartbeat regulation.
Area of Science:
- Neuroscience
- Synaptic Transmission
- Calcium Channel Physiology
Background:
- Leech heartbeat relies on reciprocally inhibitory interneurons with high- and low-threshold (HVA and LVA) Ca channels.
- LVA Ca current comprises distinct rapid (ICaF) and slow (ICaS) components crucial for graded transmission and burst formation.
Purpose of the Study:
- To differentiate the roles of ICaF and ICaS in synaptic transmission between heart interneurons.
- To investigate the interaction and relative efficacy of ICaF and ICaS in mediating graded synaptic release.
Main Methods:
- Utilized varied stimulation protocols and inorganic Ca channel blockers (e.g., Ni2+).
- Separated the functional contributions of ICaF and ICaS to synaptic transmission.
- Assessed effects on both graded and spike-mediated transmission.
Main Results:
- Ca2+ influx via ICaF is more effective for synaptic release than via ICaS.
- The rate of Ca2+ entry through LVA channels is critical for transmission.
- 1 mM Ni2+ selectively blocked LVA currents and graded transmission, sparing spike-mediated transmission.
- Both ICaF and ICaS contribute to a shared pool of releasable synaptic vesicles.
Conclusions:
- Differential efficacy of ICaF and ICaS in Ca2+ influx underlies graded synaptic transmission.
- The interplay between Ca2+ dynamics and vesicle availability governs inhibitory transmission strength.
- Multichannel domains from ICaF and radial diffusion from ICaS interact at release sites to mediate graded transmission.
Abstract:
In leeches, two pairs of reciprocally inhibitory heart interneurons that form the core oscillators of the pattern-generating network for heartbeat possess both high- and low-threshold (HVA and LVA) Ca channels. LVA Ca current has two kinetically distinct components (one rapidly activating/inactivating, ICaF, and another slowly activating/inactivating, ICaS) that mediate graded transmission, generate plateau potentials driving burst formation, and modulate spike-mediated transmission between heart interneurons. Here we used different stimulating protocols and inorganic Ca channel blockers to separate the effects of ICaF and ICaS on graded synaptic transmission and determine their interaction and relative efficacy. Ca2+ entering by ICaF channels is more efficacious in mediating release than that entering by ICaS channels. The rate of Ca2+ entry by LVA Ca channels appears to be as critical as the amount of delivered Ca2+ for synaptic transmission. LVA Ca currents and associated graded transmission were selectively blocked by 1 mM Ni2+, leaving spike-mediated transmission unaffected. Nevertheless, 1 mM Ni2+ affected homosynaptic enhancement of spike-mediated transmission that depends on background Ca2+ provided by LVA Ca channels. Ca2+ provided by both ICaF and ICaS depletes a common pool of readily releasable synaptic vesicles. The balance between availability of vesicles and Ca2+ concentration and its time course determine the strength of inhibitory transmission between heart interneurons. We argue that Ca2+ from multichannel domains arising from ICaF channels, clustered near but not directly associated with the release trigger, and Ca2+ radially diffusing from generally distributed ICaS channels interact at common release sites to mediate graded transmission.
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