Intracellular Ca2+ regulates the sensitivity of cyclic nucleotide-gated channels in olfactory receptor neurons.
In olfactory receptor neurons, odorants stimulate production of cAMP, which directly activates cyclic nucleotide-gated (CNG) channels. Olfactory adaptation is thought to result from a rise in intracellular Ca2+. To determine whether inhibition of CNG channels plays a role in adaptation, we have investigated the action of Ca2+ on these channels in inside-out "macro" patches from the dendrite and cilia of catfish olfactory neurons. Internal Ca2+, with a K1/2 of 3 microM, profoundly inhibits CNG channels by shifting the dose-response relationship to higher cAMP levels without altering the maximal response. The inhibition does not appear to result from a direct interaction of Ca2+ with the CNG channel. Thus, the inhibition washes out after excision of the inside-out patch, and Ca2+ does not inhibit the cloned catfish CNG channel expressed in Xenopus oocytes. Hence we propose that a regulatory Ca(2+)-binding protein, distinct from the CNG channel, controls the gain of signal transduction and contributes to olfactory adaptation by decreasing the sensitivity of the CNG channel to cAMP.
Kramer
R H
RH
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Siegelbaum
S A
SA
D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000494:pharmacology*; D004553:Electric Conductivity; D015870:Gene Expression; D007059:Ictaluridae; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D009474:Neurons / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D012903:Smell / Q000502:physiology*; D014162:Transfection; D014981:Xenopus
D007473:Ion Channels; D000242:Cyclic AMP; D002118:Calcium