Activation of M₁muscarinic acetylcholine receptors (M₁mAChR) 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_qgene.PTX-insensitive M₁mAChR inhibition ofI_Cawas strongly reduced in Gα_q−/− mouse SCG neurons and was fully restored by acute overexpression of Gα_q. In contrast, M₁mAChR inhibition ofI_K(M)persisted in Gα_q−/− mouse SCG cells. However, unlike rat SCG neurons, muscarinic inhibition ofI_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/11antibodies.Bradykinin (BK) also inhibitsI_K(M)in rat SCG neurons via a PTX-insensitive G-protein (G_qand/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/11antibody.We conclude that, in mouse SCG neurons (1) M₁mAChR inhibition ofI_Cais mediated principally by G_q, (2) M₁mAChR inhibition ofI_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 ofI_K(M)is mediated wholly by G₁₁.