M-channels in rat (Wang et al. 1998; Hadley et al. 2003) and mouse (Selyanko et al. 1999) SCG neurons are most likely composed primarily of Kv7.2 and 7.3 subunits of the Kv7 potassium channel family. However, since all Kv7 subunits can generate ‘M-like’ currents (Selyanko et al. 2000), and since rat SCG neurones express three Kv7 subunits (Kv7.2, 7.3 and 7.5: Hadley et al. 2003), we have used Kv7.2 gene-deleted mice (Watanabe et al. 2000) to further assess the contribution of this particular subunit to M-channels in SCG neurones. Homozygote Kv7.2-null mice do not survive after birth, so we used neurones from SCGs isolated from E17 embryos and cultured for 1-2 days in vitro. M-currents (I_M) were measured in neurones from wild-type (+/+), heterozygous (+/-) and homozygous (-/-) gene-deleted embryos using amphotericin-perforated patch pipettes (see Hadley et al. 2003). Double gene-deletion totally eliminated M-current expression. Thus, sustained outward currents recorded at -20 mV holding potential were significantly (P<0.05, ANOVA) reduced from 12.6 ± 2.1 pA pF^-1 (n=18) in +/+ cells to 4.7 ± 1.6 pA pF^-1 (n=17) in -/- cells, and no deactivation I_M-tails could be detected in -/- cells on stepping to -50 mV. Further, the M-channel enhancer retigabine (10 μM) increased outward currents in +/+ cells, but not in -/- cells. Single gene-deletion partly reduced I_M. Retigabine produced significantly (P<0.05, ANOVA) less increase in the standing outward current at -20 mV in +/- cells and the deactivation tail-current at -50 mV was reduced by ~60% (4.5 ± 1.1 pA pF^-1 (n=18) in +/+ cells; 1.8 ± 0.2 pA pF^-1 (n=33) in +/- cells). Further, this residual current was less sensitive to tetraethylammonium (TEA) than that in +/+ cells (tail-current reduction by 10 mM TEA being 91.6 ± 3.5% (n=9) in +/+ cells and 56.2 ± 8.3% (n=7) in +/- cells). This suggests some substitution of TEA-sensitive Kv7.2 subunits by TEA-insensitive subunits such as Kv7.5 in +/- mouse embryos (see Hadley et al. 2003). These results accord with an obligatory contribution of Kv7.2 subunits to embryonic M-channel formation. Cells from gene-deleted mice were also hyper-excitable, so reduced I_M might explain the seizures that occur in human neonates with Kv7.2 mutations.