TABLE 1.

Inhibition of baclofen-sensitive Ba2+ current (% Ipeptide/Ibaclofen) mediated by WT and mutant GABABR-coupled Cav2.2 channels expressed in HEK293T cells by α-conotoxins Vc1.1, RgIA, and PeIA. Whole-cell IBa mediated by the double mutant S130A + S153A was inhibited by the selective Cav2.2 antagonist, ω-conotoxin CVIE (100 nM).

GABABR mutantsVc1.1Rg1APeIA
WT-GABABR59 ± 4 (11)a54 ± 3 (11)a58 ± 3 (11)a
B1 subunit
S130A33 ± 4 (9)b31 ± 7 (5)b38 ± 3 (5)b
S131A39 ± 5 (6)b40 ± 5 (5)b16 ± 4 (6)b
S153A12 ± 2 (9)c13 ± 3 (5)c19 ± 1 (5)c
S154A17 ± 2 (5)c16 ± 5 (5)c28 ± 5 (5)b
S130A + S153A11 ± 2 (9)d11 ± 3 (5)d7 ± 2 (5)d
R162A19 ± 4 (5)c9 ± 1 (5)c16 ± 2 (5)c
T198A30 ± 2 (5)b31 ± 1 (5)b30 ± 2 (5)b
E200A22 ± 4 (5)b17 ± 5 (5)c16 ± 2 (5)c
E253A23 ± 5 (5)b26 ± 4 (5)b43 ± 7 (5)b
F227A23 ± 3 (5)b16 ± 3 (5)c19 ± 3 (5)c
D380A52 ± 2 (5)a47 ± 4 (5)a46 ± 4 (5)a
B2 subunit
R89A46 ± 3 (5)a51 ± 4 (5)a48 ± 4 (5)a
D165A27 ± 4 (5)b31 ± 2 (5)b30 ± 1 (5)b
K168A15 ± 5 (5)c21 ± 3 (6)b9 ± 3 (5)c
R207A20 ± 5 (5)b16 ± 3 (5)c14 ± 3 (5)c
  • aMaximum inhibition (>45%) of WT and mutant GABABR-coupled Cav2.2 channels by baclofen (50 μM) and α-conotoxins (1 μM)

  • bReduced inhibition (20%–45%) of baclofen-sensitive current

  • cSignificantly reduced inhibition (<20%) of baclofen-sensitive current

  • dNo inhibition of baclofen-sensitive current