Next, we tested the effects of deletion of the CLZ domain (amino acids 609-693) of the CNGA1 subunit (CNGA1-∆CLZ). Deletion of the CLZ domain had no effect on the expression or measured functional properties of CNGA1-∆CLZ homomeric channels (Fig. 2a) 21 . However, it had a dramatic effect on expression and functional properties of CNGA1-∆CLZ + CNGB1 heteromeric channels. As shown previously, co-expression of CNGA1-∆CLZ with CNGB1 at a typical 1:4 RNA ratio virtually eliminated all functional channel expression (Fig. 2a) 21 . This dominant negative effect may underlie one form of retinitis pigmentosa resulting from deletion of a portion of the CLZ domain in CNGA1 (refs 21,22) and suggests that the CNGA1-∆CLZ channels are still interacting with CNGB1, perhaps in an uncontrolled manner. To recover functional expression of heteromeric channels, we co-injected CNGA1-∆CLZ with CNGB1-∆N containing a deletion of the trafficking signal in the amino-terminal region of CNGB1 (ref. 21) . Even at an RNA ratio of 1:2 CNGA1-∆CLZ: CNGB1-∆N, the effect of the CLZ domain deletion on the heteromeric channels was striking. Co-expression of CNGA1-∆CLZ and CNGB1-∆N yielded channels with a highly elevated cAMP efficacy (I cAMP /I cGMP = 0.38 ± 0.02, n = 10) (Fig. 2a) , significantly higher than CNGA1 homomeric channels and CNGA1 + CNGB1 heteromeric channels (Fig. 2b) . The elevated cAMP efficacy seen with the CLZ domain deletion in heteromeric channels, but not homomeric channels, suggests the possibility that CNGA1-∆CLZ and CNGB1-∆N form heteromeric channels with a novel stoichiometry, perhaps with more than one CNGB1 subunit per channel.