M. Kinoshita et al., Binding of G alpha(o) N terminus is responsible for the voltage-resistant inhibition of alpha(1A)(P/Q-type, Ca(v)2.1) Ca2+ channels, J BIOL CHEM, 276(31), 2001, pp. 28731-28738
G-protein-mediated inhibition of presynaptic voltage-dependent Ca2+ channel
s is comprised of voltage-dependent and -resistant components. The former i
s caused by a direct interaction of Ca2+ channel alpha1 subunits with G bet
a gamma, whereas the latter has not been characterized well. Here, we show
that the N terminus of G alpha (o), is critical for the interaction with th
e C terminus of the alpha (1A) channel subunit, and that the binding induce
s the voltage-resistant inhibition. An alpha (1A) C-terminal peptide, an an
tiserum raised against G alpha (o) N terminus, and a G alpha (o) N-terminal
peptide all attenuated the voltage-resistant inhibition of alpha (1A) curr
ents. Furthermore, the N terminus of G alpha (o) bound to the C terminus of
alpha (1A) in vitro, which was prevented either by the alpha (1A) channel
C-terminal or G alpha (o) N-terminal peptide. Although the C-terminal domai
n of the alpha (1B) channel showed similar ability in the binding with G al
pha (o) N terminus, the above mentioned treatments were ineffective in the
alpha (1B) channel current. These findings demonstrate that the voltage-res
istant inhibition of the P/Q-type, alpha (1A) channel is caused by the inte
raction between the C-terminal domain of Ca2+ channel alpha (1A) subunit an
d the N-terminal region of G alpha (o).