Regulation of voltage sensing structures of CaV1.2 calcium channel by the auxiliary β-subunit
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2023-04
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Universidad de Valparaíso
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Programa de Doctorado en Ciencias con Mención Neurociencia
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Voltage-gated Calcium Channels (CaV) are the main entryway for calcium influx into excitable cells. High Voltage-gated Calcium Channels (HVA) have four homologous but nonidentical repeats encompassing a voltage-sensing domain (VSD) and a quarter of the pore. In a physiological context, HVA can be modulated at least by two accessory subunits 2, and . In 1993, Neely et al. reported that CaV subunits could facilitate channel opening without altering gating currents' voltage dependence, suggesting that the energetic interaction between voltage sensors and the pore is modified.
I tested this hypothesis using the Voltage Clamp Fluorometry technique to track the movement of human CaV1.2 individual VSDs in the presence or absence of CaV subunits. I expressed 1c pore-forming subunit with 2-1 in Xenopus oocytes and used the cut-open technique to implement voltage-clamp. I found that CaV modulates mostly VSD II with negligible impact on VSD III and VSD IV behavior and that this VSDII is moving in two steps.
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CANALES DE CALCIO, SENSORES, FLUOROMETRIA