Journal article
CaV2.1 α1 subunit motifs that control presynaptic CaV2.1 subtype abundance are distinct from CaV2.1 preference
The Journal of physiology, Vol.602(3), pp.485-506
02/01/2024
DOI: 10.1113/JP284957
PMCID: PMC10872416
PMID: 38155373
Appears in UI Libraries Support Open Access
Abstract
Presynaptic voltage-gated Ca2+ channel (Ca-V) subtype abundance at mammalian synapses regulates synaptic transmission in health and disease. In the mammalian central nervous system (CNS), most presynaptic terminals are Ca(V)2.1 dominant with a developmental reduction in Ca(V)2.2 and Ca(V)2.3 levels, and Ca(V)2 subtype levels are altered in various diseases. However, the molecular mechanisms controlling presynaptic Ca(V)2 subtype levels are largely unsolved. Because the Ca(V)2 alpha(1) subunit cytoplasmic regions contain varying levels of sequence conservation, these regions are proposed to control presynaptic Ca(V)2 subtype preference and abundance. To investigate the potential role of these regions, we expressed chimeric Ca(V)2.1 alpha(1) subunits containing swapped motifs with the Ca(V)2.2 and Ca(V)2.3 alpha(1) subunit on a Ca(V)2.1/Ca(V)2.2 null background at the calyx of Held presynaptic terminals. We found that expression of Ca(V)2.1 alpha(1) subunit chimeras containing the Ca(V)2.3 loop II-III region or cytoplasmic C-terminus (CT) resulted in a large reduction of presynaptic Ca2+ currents compared to the Ca(V)2.1 alpha(1) subunit. However, the Ca2+ current sensitivity to the Ca(V)2.1 blocker agatoxin-IVA was the same between the chimeras and the Ca(V)2.1 alpha(1) subunit. Additionally, we found no reduction in presynaptic Ca2+ currents with Ca(V)2.1/2.2 cytoplasmic CT chimeras. We conclude that the motifs in the Ca(V)2.1 loop II-III and CT do not individually regulate Ca(V)2.1 preference, although these motifs control Ca(V)2.1 levels and the Ca(V)2.3 CT contains motifs that negatively regulate presynaptic Ca(V)2.3 levels. We propose that the motifs controlling presynaptic Ca(V)2.1 preference are distinct from those regulating Ca(V)2.1 levels and may act synergistically to impact pathways regulating Ca(V)2.1 preference and abundance.
Details
- Title: Subtitle
- CaV2.1 α1 subunit motifs that control presynaptic CaV2.1 subtype abundance are distinct from CaV2.1 preference
- Creators
- Jianing Li - Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52240 USAPriyadharishini Veeraraghavan - Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52240 USASamuel M Young Jr - University of Iowa, Iowa Neuroscience Institute
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.602(3), pp.485-506
- DOI
- 10.1113/JP284957
- PMID
- 38155373
- PMCID
- PMC10872416
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Publisher
- Wiley
- Number of pages
- 22
- Grant note
- National Institute on Deafness and Other Communication Disorders. Grant Number: R01 DC014093 National Institute of Neurological Disorders and Stroke. Grant Number: R01 NS110742 National Center for Advancing Translational Sciences. Grant Number: R03TR004161-01 University of Iowa. Grant Number: N/A American Heart Association. Grant Number: 23PRE1019152
- Language
- English
- Electronic publication date
- 12/28/2023
- Date published
- 02/01/2024
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984550559702771
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