RAPID APPLICATION AND REMOVAL OF 2ND MESSENGERS TO CYCLIC NUCLEOTIDE-GATED CHANNELS FROM OLFACTORY EPITHELIUM

The last step in the second-messenger cascade mediating vertebrate olf actory transduction is the direct opening of a nonspecific cation chan nel by cAMP. The kinetic properties of this interaction are critical i n determining the time course of the sensory response. To analyze thes e properties, excised inside-out membrane patches containing either th e native channel from salamander olfactory-receptor neurons or a recom binant rat olfactory cyclic nucleotide-gated channel were exposed to s hort pulses of known concentrations of cAMP or cGMP to mimic a rapid a nd transient production of second messenger. Channel activity outlaste d cyclic nucleotide pulses for several hundred milliseconds. This effe ct was due to an intrinsic property of the olfactory channel protein b ecause it did not occur with cGMP-activated channels from retinal phot oreceptors. Gating kinetics of the olfactory channel were both voltage and agonist dependent. These results demonstrate that the overall slo w channel-gating kinetics could account for the difference in time cou rse between the odor-induced changes in cAMP concentration and the sub sequent sensory generator current.