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- W1963550243 abstract "Gating of voltage-dependent calcium channels (Cav) is determined by S4 segments in each of the four α1-subunit domain's. In the S4 segments, also known as voltage sensors, every third position there is a positive charged residue (lysine or arginine). However, both high-voltage (HVA) and low-voltage (LVA or T-type) activated Cav channels, show S4 segments with very similar sequences. This issue had already been investigated in some members of T-type Cav3 family, mainly in Cav3.1 (α1G), and one report on Cav3.2 (α1H), but there is no data on the Cav3.3 (α1I). To investigate the role of S4 segments in the differences in gating between Cav3.3 and Cav1.2 we made a chimerical approach swapping the S4 segment of domain II of Cav3.3 with the corresponding S4 segment of Cav1.2. We have used HEK-293 cells and the whole-cell patch clamp technique to characterize the functional expression of the constructs. Our preliminary results indicate that the substitution of the IIS4 segment of Cav3.3 for that of Cav1.2 induce a 25 mV positive shift in the I-V peak with respect to the Cav3.3 wild type (WT). Also, the Boltzmann parameters were significantly different between the WT and the chimeric channel I-V curves. There was no appreciable change in the kinetics of the currents. An unexpected result was a drastic decrease (< 95%) in the current density of the chimeric channel. A possible explanation is that the IIS4 (the whole or some residues of it) of Cav1.2 is interacting with the rest of the channel protein in such way that makes more stable the closed state of the channel. Additional experiments are under way to further study this observation.This work was supported by CONACYT Mexico J50250Q." @default.
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- W1963550243 date "2009-02-01" @default.
- W1963550243 modified "2023-10-03" @default.
- W1963550243 title "Role of S4 segments in Cav1 and Cav3 channels: gating and current density" @default.
- W1963550243 doi "https://doi.org/10.1016/j.bpj.2008.12.864" @default.
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