Activation of M₁ muscarinic acetylcholine receptors (M₁ mAChR) inhibits M-type potassium currents (I_(K(M))) and N-type calcium currents (I_(Ca)) in mammalian sympathetic ganglia. Previous antisense experiments suggested that, in rat superior cervical ganglion (SCG) neurons, both effects were partly mediated by the G-protein Gα_q (Delmas et al., 1998a; Haley et al., 1998a), but did not eliminate a contribution by other pertussis toxin (PTX)-insensitive G-proteins. We have tested this further using mice deficient in the Gα_q gene.
PTX-insensitive M₁ mAChR inhibition of I_(Ca) was strongly reduced in Gα_q −/− mouse SCG neurons and was fully restored by acute overexpression of Gα_q. In contrast, M₁mAChR inhibition of I_(K(M)) persisted in Gα_q−/− mouse SCG cells. However, unlike rat SCG neurons, muscarinic inhibition of I_(K(M)) was partly PTX-sensitive. Residual (PTX-insensitive)I_(K(M)) inhibition was slightly reduced in Gα_q −/− neurons, and the remaining response was then suppressed by anti-Gα_(q/11) antibodies.
Bradykinin (BK) also inhibits IK(M) in rat SCG neurons via a PTX-insensitive G-protein (G_q and/or G₁₁; Jones et al., 1995). In mouse SCG neurons, I_(K(M)) inhibition by BK was fully PTX-resistant. It was unchanged in Gα_q −/− mice but was abolished by anti-Gα_(q/11) antibody.
We conclude that, in mouse SCG neurons (1) M₁ mAChR inhibition of I_(Ca) is mediated principally by G_q, (2) M₁ mAChR inhibition of I_(K(M)) is mediated partly by G_q, more substantially by G₁₁, and partly by a PTX-sensitive G-protein(s), and (3) BK-induced inhibition of I_(K(M)) is mediated wholly by G₁₁
