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

Abstract：

: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 microM). 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 microM, 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.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Satoh TO,Yamada M

doi

10.1016/s0028-3908(99)00207-5

subject

Has Abstract

pub_date

2000-04-27 00:00:00

pages

1284-91

issue

7

eissn

0028-3908

issn

1873-7064

pii

S0028390899002075

journal_volume

39

pub_type

杂志文章

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