Blocking adenylyl cyclase inhibits olfactory generator currents induced by"IP3-odors"

Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into el ectrical signals by means of an adenylyl cyclase/cAMP second messenger casc ade, but it remains widely debated whether this cAMP cascade mediates trans duction for all odorants or only certain odor classes. To address this prob lem, we have analyzed the generator currents induced by odors that failed t o produce cAMP in previous biochemical assays but instead produced IP3 ("IP 3-odors"). We show that in single salamander ORNs, sensory responses to "cA MP-odors" and IP3-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP3-odors exhibit identical biophysical prop erties as those induced by cAMP odors or direct activation of the cAMP casc ade. By disrupting adenylyl cyclase to block cAMP formation using two poten t antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP3-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhi bition of adenylyl cyclase prevents EOG responses to both odor classes in m ouse MOE, even when "hot spots" with heightened sensitivity to IP3-odors ar e examined.