Cyclic AMP links amino acid chemoreceptors to ion channels in olfactory cilia

Abstract
Amino acids, olfactory stimuli for the channel catfish (Ictalurus punctatus), were tested for the ability to affect cyclic AMP metabolism in isolated olfactory cilia. Ten stimuli, representative of each receptor subtype and covering a wide range of electrophysiological potency, elicited similar increases in guanine nucleotide-dependent cyclic AMP formation. Stimulus-dependent activation of adenylate cyclase was observed only when receptor occupancy approached or exceeded 50%. Stimulus activation of adenylate cyclase was additive with that obtained with guanine nucleotide alone, was independent of receptor specificity, and poorly correlated with neural potency. Stimuli did not affect cyclic nucleotide phosphodiesterase activity in isolated cilia preparations. Both cyclic AMP and cyclic GMP reversibly increased membrane conductance in isolated ciliary membranes incorporated in artificial phospholipid bilayers. The cyclic nucleotide-gated conductance was activated by either nucleotide with equal potency, did not require exogenous ATP or GTP, and was mediated by 44 pS non-selective cation channels. Taken together, these results suggest that, under appropriate conditions of receptor occupancy, cyclic AMP links amino acid chemoreceptor binding to membrane depolarization by directly gating cation channels in olfactory cilia.