A bradycardiac agent ZD7288 blocks the hyperpolarization-activated current ( Ih) in retinal rod photoreceptors

Recently it has been reported that “ I f channel blockers”, which block the hyperpolarization-activated inward current ( I f) in heart sino atrial node cells, also block the hyperpolarization-activated inward current ( I h) in other tissues. Here we compared the effects of one of these agents, ZD728...

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Bibliographic Details
Published in:Neuropharmacology 2000-06, Vol.39 (7), p.1284-1291
Main Authors: Satoh, Tomo-Oki, Yamada, Masahiro
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cardiotonic Agents - pharmacology
Cesium - pharmacology
Frog
In Vitro Techniques
Medical sciences
Membrane Potentials - drug effects
Membrane Potentials - physiology
Miscellaneous
Newt
Patch-Clamp Techniques
Pharmacology. Drug treatments
Photic Stimulation
Potassium Channel Blockers
Pyrimidines - pharmacology
Rana catesbeiana
Retina
Retina - drug effects
Retinal Rod Photoreceptor Cells - drug effects
Rod photoreceptors
Salamandridae
Sodium Channel Blockers
ZD7288
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Summary:Recently it has been reported that “ I f channel blockers”, which block the hyperpolarization-activated inward current ( I f) in heart sino atrial node cells, also block the hyperpolarization-activated inward current ( I h) in other tissues. Here we compared the effects of one of these agents, ZD7288 [4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride], with those of Cs + on I h in amphibian rod photoreceptors using patch clamp and intracellular recordings. ZD7288 strongly inhibited I h in newt rod photoreceptors in a concentration-dependent manner (1–100 μM). ZD7288 exerted a blocking action on the conductance of I h with no alteration of its gating properties, and the blocking action of I h was not use-dependent. At concentrations as low as 1 μM, ZD7288 markedly enhanced the hyperpolarizing membrane responses of frog rod photoreceptors to bright light and delayed the response recovery, indicating that ZD7288 is highly selective for I h. The apparent effect of the drug was slow in onset and irreversible, suggesting that ZD7288 act at a cytosolic site on the I h channel. These observations also confirm the involvement of I h in accelerating the response recovery process from deep membrane hyperpolarization induced by bright light in rod cells.
ISSN:0028-3908
1873-7064
DOI:10.1016/S0028-3908(99)00207-5