To determine the role of the CLZ domain in controlling heteromeric assembly of CNGA1 + CNGB1 channels, we first measured the functional effects of deleting the CLZ domain. CNG channels were expressed in Xenopus oocytes and studied using the inside-out configuration of the patch-clamp technique. Homomeric channels of CNGA1 subunits are efficiently activated by saturating cGMP, but poorly activated by saturating cAMP (I cAMP /I cGMP = 0.05 ± 0.01, n = 6) (Fig. 2a , black is with 2.5 mM cGMP, red is with 16 mM cAMP). However, incorporation of a single CNGB1 subunit per tetramer confers a significant elevation in cAMP efficacy (I cAMP / I cGMP = 0.22 ± 0.03, n = 7) (Fig. 2a) . The mechanism of the increased cAMP efficacy by the CNGB1 subunit is unknown but could involve either cAMP binding to CNGB1 or simply a more favourable opening transition with CNGB1 (or both). This increased efficacy is constant over a wide range of CNGB1 expression levels, indicating that the CNGB1 subunit incorporates into the channel with a fixed and tightly-regulated stoichiometry 15 .