Inhibition of olfactory cyclic nucleotide-activated current by calmodulin antagonists

1. In amphibian olfactory receptor neurones, much of the depolarizing current in response to odours is carried by cationic channels that are directly gated by cyclic AMP. The effects of four calmodulin antagonists on the cyclic AMP-activated receptor current were studied in single olfactory cilia of the frog. 2. Two antagonists, W-7 and trifluoperazine, were potent and reversible inhibitors of the cyclic AMP-activated current. IC50 values were 5 microM for W-7 and 13 microM for trifluoperazine. A third antagonist, calmidazolium, irreversibly blocked the current. The fourth, mastoparan, had little effect. 3. Calmodulin was unable to reverse the effects of W-7 and trifluoperazine, suggesting that these inhibitors act directly on the cyclic AMP-gated channels. 4. Neither W-7 nor trifluoperazine inhibited a Ca(2+)-activated Cl- current which also contributes to the odorant response. These compounds thus allow the two components of the olfactory receptor current to be discriminated.