PMID- 8989388
OWN - NLM
STAT- MEDLINE
DCOM- 19970204
LR  - 20171213
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 74
IP  - 4
DP  - 1995 Oct
TI  - Regulation of cyclic nucleotide-gated channels and membrane excitability in 
      olfactory receptor cells by carbon monoxide.
PG  - 1498-508
AB  - 1. The effect of the putative neural messenger carbon monoxide (CO) and the role 
      of the cGMP second-messenger system for olfactory signal generation was examined 
      in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. With 
      the use of whole cell voltage-clamp recordings in combination with a series of 
      ionic and pharmological tests, it is demonstrated that exogenously applied CO is 
      a potent activator (K1/2 = 2.9 microM) of cyclic nucleotide-gated (CNG) channels 
      previously described to mediate odor transduction. 3. Several lines of evidence 
      suggest that CO mediates its effect through stimulation of a soluble guanylyl 
      cyclase (sGC) leading to formation of the second-messenger cGMP. This conclusion 
      is based on the findings that CO responses show an absolute requirement for 
      guanosine 5'-triphosphate (GTP) in the internal solution, that no direct effect 
      of CO on CNG currents in the absence of GTP is detectable, and that a blocker of 
      sGC activation, LY85383 (10 microM), completely inhibits the CO response. 4. The 
      dose-response curve for cGMP at CNG channels is used as a calibration to provide 
      a quantitative estimate of the CO-stimulated cGMP formation. This analysis 
      implies that CO is a potent activator of olfactory sGC. 5. Perforated patch 
      recordings using amphotericin B demonstrate that low micromolar doses of CO 
      effectively depolarize the membrane potential of ORNs through tonic activation of 
      CNG channels. This effect in turn regulates excitable and adaptive properties of 
      ORNs and modulates neuronal responsiveness. 6. These data argue for an important 
      role of the cGMP pathway in olfactory signaling and support the idea that CO may 
      function as a diffusible messenger in the olfactory system.
FAU - Leinders-Zufall, T
AU  - Leinders-Zufall T
AD  - Section of Neurobiology, Yale University School of Medicine, New Haven, 
      Connecticut 06510, USA.
FAU - Shepherd, G M
AU  - Shepherd GM
FAU - Zufall, F
AU  - Zufall F
LA  - eng
GR  - R01 DC-00086/DC/NIDCD NIH HHS/United States
GR  - R01 DC-02227/DC/NIDCD NIH HHS/United States
GR  - R01-MH-52550/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Ion Channels)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Adaptation, Physiological
MH  - Animals
MH  - Carbon Monoxide/*pharmacology
MH  - Cell Membrane/physiology
MH  - Cyclic GMP/*physiology
MH  - Electrophysiology
MH  - Guanylate Cyclase/metabolism
MH  - Ion Channel Gating
MH  - Ion Channels/*drug effects/metabolism
MH  - Neurons, Afferent/*drug effects/metabolism/*physiology
MH  - Olfactory Pathways/cytology/metabolism/*physiology
MH  - Patch-Clamp Techniques
MH  - Urodela
OTO - NASA
OT  - NASA Discipline Neuroscience
OT  - Non-NASA Center
FIR - Shepherd, G M
IR  - Shepherd GM
IRAD- Yale U, New Haven, CT
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - 10.1152/jn.1995.74.4.1498 [doi]
PST - ppublish
SO  - J Neurophysiol. 1995 Oct;74(4):1498-508. doi: 10.1152/jn.1995.74.4.1498.