Block of Cyclic Nucleotide-Gated Channel s in Salamander Olfactory
Receptor Neurons by the Guanylyl Cyclase Inhibitor LY83583.
Leinders-Zufall, Trese and Frank Zufall.
Section of Neurobiology, Yale University School of Medicine, New Haven,
Connecticut 06510.
APStracts 2:0283N, 1995.
SUMMARY AND CONCLUSIONS
1. Using whole-cell voltage clamp recordings the guanylyl cyclase inhibitor
LY83583 [6-(phenylamino)-5,8-quinolinedione] is shown to act as a potent
blocker of cyclic nucleotide-gated (CNG) channels in isolated olfactory
receptor neurons (ORNs) of the tiger salamander. 2. Under our experimental
conditions, onset of the blockade by LY83583 occurs on the time scale of
seconds and is completely reversed upon wash-out of the drug. Dose-response
curves reveal a K d of 1.4 [mu]M (at -60 mV). Other data suggest that LY83583
acts within the CNG channel pore and that the channels must be in an activated
state before the drug can exert its effect. 3. It appears that LY83583 can act
on both CNG channels and soluble guanylyl cyclase (sGC) and that these two
effects can be distinguished by their different recovery behaviors. While the
LY83583-induced blockade of CNG channels activated directly by cGMP is rapidly
reversible (with a recovery time constant of ¦ 3 s), previous results have
shown that no recovery is obtained during minute-long washing periods when the
channels are activated indirectly through exogenous carbon monoxide
application, which acts as a stimulator of sGC in ORNs. 4. LY83583 appears to
be a novel and useful agent in examining neural functions due to CNG channel
responses.
Received 12 July 1995; accepted in final form 12 September 1995.
APS Manuscript Number J441-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.