The idea of having two second pathways In ofa , one mediated by cAMP aNd the other by bnosytol 1,4,5-trispbosphate, Is tation and inhibition of lobster ORNs are mediated by InsP3 and cAMP transduction cascades would be to demonstrate the presence of InsP3-and cAMP-activated ion channels at the presumed site of transduction, the outer dendritic membrane, in lobster ORNs in situ.Here, we report that cAMP and InsP3 applied to the inner face of cell-free patches of the outer dendritic membrane of lobster ORNs in situ directly activate distinct ion channels, that both types of second messenger-gated channels can occur in the same patch, and that the InsP3-gated channels, and possibly the cAMP-gated channels, can be one of two types. A preliminary description of these results has appeared (24).Odors are generally thought to activate olfactory receptor neurons (ORNs) through guanine nucleotide binding proteincoupled receptors that elicit rapid and transient pulses of intracellular second messengers (for reviews, see refs. 1-3). Attention has focused on two second messenger pathways, one mediated by cAMP and the other by inositol 1,4,5-trisphosphate (InsP3). cAMP and InsP3 olfactory transduction cascades have been identified in four groups of animals (mammals, refs. 4-6; amphibians, refs. 7 and 8; fish, refs. 9 and 10; crustaceans, refs. 11 (25), so the excised tips should contain only outer dendritic membrane and microtubules. Care was taken to include <50% of the length of the sensillum in the excised tips. Outer dendrites were placed in poly(D-lysine)-coated plastic dishes containing 5 ml of isolation buffer (460 mM