Year: 2025
Type: article
Abstract: Depolarization-evoked opening of Ca V 2.1 (P/Q-type) Ca 2+ -channels triggers neurotransmitter release, while voltage-dependent inactivation (VDI) limits channel availability to open, contributing to synaptic plasticity. The mechanism of Ca V 2.1 response to voltage is unclear. Using voltage-clamp fluorometry and kinetic modeling, we optically tracked and physically characterized the structural dynamics of the four Ca V 2.1 voltage-sensor domains (VSDs). VSD-I seems to directly drive opening and convert between two modes of function, associated with VDI. VSD-II is apparently voltage-insensitive. VSD-III and VSD-IV sense more negative voltages and undergo voltage-dependent conversion uncorrelated with VDI. Auxiliary β-subunits regulate VSD-I-to-pore coupling and VSD conversion kinetics. Ca V 2.1 VSDs are differentially sensitive to voltage changes brief and long-lived. Specifically the voltage-dependent conformational changes of VSD-I are linked to synaptic release and plasticity.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1524352559, G1792340361, Molecular physiology and regulation of presynaptic calcium channels, G2718091676, The molecular movements that convert electrical to Ca2+ signaling in the presynaptic terminal, G444442740, POTASSIUM CHANNEL OPENERS AS AN HYPEREXCITABILITY-REDUCING STRATEGY, The Molecular Transitions that Initiate EC Coupling in Skeletal Muscle
OpenAlex ID: W4409725812