TY - JOUR
T1 - Selective regulation of N-type Ca channels by different combinations of G-protein β/γ subunits and RGS proteins
AU - Zhou, J. Y.
AU - Siderovski, D. P.
AU - Miller, R. J.
PY - 2000/10/1
Y1 - 2000/10/1
N2 - We examined the effects of G-protein β and γ subunit heterodimers on human α(1B) (N-type) Ca channels expressed in HEK293 cells. All of the known β subunits (β1-β5) produced voltage-dependent inhibition of α(1B) Ca channels, depending on the γ subunit found in the heterodimer. β1-β4 subunits inhibited Ca channels when paired with γ1-γ3. However, β5 subunits only produced inhibition when paired with γ2. In contrast, hererodimers between β5 subunits and RGS (regulators of G-protein signaling) proteins containing GGL domains did not produce inhibition of Ca channels. However, GGL domain-containing RGS proteins (e.g., RGS6 and RGS11) did block the ability of Gβ5/γ2 heterodimers to inhibit Ca channels. Because all of the G-protein β subunits are found in the nervous system, we conclude that they may all potentially participate in Ca channel inhibition. The interaction of GGL-containing RGS proteins with Gβ5γ2 suggests a novel way in which Ca channels can be regulated.
AB - We examined the effects of G-protein β and γ subunit heterodimers on human α(1B) (N-type) Ca channels expressed in HEK293 cells. All of the known β subunits (β1-β5) produced voltage-dependent inhibition of α(1B) Ca channels, depending on the γ subunit found in the heterodimer. β1-β4 subunits inhibited Ca channels when paired with γ1-γ3. However, β5 subunits only produced inhibition when paired with γ2. In contrast, hererodimers between β5 subunits and RGS (regulators of G-protein signaling) proteins containing GGL domains did not produce inhibition of Ca channels. However, GGL domain-containing RGS proteins (e.g., RGS6 and RGS11) did block the ability of Gβ5/γ2 heterodimers to inhibit Ca channels. Because all of the G-protein β subunits are found in the nervous system, we conclude that they may all potentially participate in Ca channel inhibition. The interaction of GGL-containing RGS proteins with Gβ5γ2 suggests a novel way in which Ca channels can be regulated.
KW - Calcium channel
KW - Heterotrimeric G-proteins
KW - Ionchannel modulation
KW - Presynaptic inhibition
KW - RGS proteins
KW - Synaptic transmission
UR - http://www.scopus.com/inward/record.url?scp=0034307596&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.20-19-07143.2000
DO - 10.1523/jneurosci.20-19-07143.2000
M3 - Article
C2 - 11007869
AN - SCOPUS:0034307596
SN - 0270-6474
VL - 20
SP - 7143
EP - 7148
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 19
ER -