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• W2113130197 abstract "We have examined the basis for G-protein modulation of the neuronal voltage-dependent calcium channels (VDCCs) α1E and α1B. A novel PCR product of α1E was isolated from rat brain. This contained an extended 5′ DNA sequence and was subcloned onto the previously cloned isoform rbEII, giving rise to α1E long whose N terminus was extended by 50 amino acids. VDCC α1 subunit constructs were co-expressed with the accessory α2-δ and β2a subunits in Xenopus oocytes and mammalian (COS-7) cells. The α1E long showed biophysical properties similar to those of rbEII; however, when G-protein modulation of expressed α1 subunits was induced by activation of co-expressed dopamine (D2) receptors with quinpirole (100 n m ) in oocytes, or by co-transfection of Gβ1γ2 subunits in COS-7 cells, α1E long , unlike α1E(rbEII), was found to be G-protein-modulated, in terms of both a slowing of activation kinetics and a reduction in current amplitude. However, α1E long showed less modulation than α1B, and substitution of the α1E 1–50 with the corresponding region of α1B 1–55 produced a chimera α1bEEEE, with G-protein modulation intermediate between α1E long and α1B. Furthermore, deletion of the N-terminal 1–55 sequence from α1B produced α1BΔN 1–55 , which could not be modulated, thus identifying the N-terminal domain as essential for G-protein modulation. Taken together with previous studies, these results indicate that the intracellular N terminus of α1E 1–50 and α1B 1–55 is likely to contribute to a multicomponent site, together with the intracellular I–II loop and/or the C-terminal tail, which are involved in Gβγ binding and/or in subsequent modulation of channel gating." @default.
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• W2113130197 date "1998-07-01" @default.
• W2113130197 modified "2023-10-17" @default.
• W2113130197 title "Identification of the Amino Terminus of Neuronal Ca²⁺Channel α1 Subunits α1B and α1E as an Essential Determinant of G-Protein Modulation" @default.
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• W2113130197 doi "https://doi.org/10.1523/jneurosci.18-13-04815.1998" @default.
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