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A bradycardiac agent ZD7288 blocks the hyperpolarization-activated current (I(h)) in retinal rod photoreceptors
Insights
ZD7288 blocks the hyperpolarization-activated inward current (I(h)) in rod photoreceptors. This agent selectively inhibits I(h), confirming its role in visual response recovery.
Area of Science:
- Neuroscience
- Cellular Physiology
Background:
- Hyperpolarization-activated inward current (I(h)) is present in various tissues.
- I(f) channel blockers, like ZD7288, may also affect I(h).
Purpose of the Study:
- To compare the effects of ZD7288 and Cs(+) on I(h) in amphibian rod photoreceptors.
- To investigate the role of I(h) in the recovery of rod photoreceptor responses.
Main Methods:
- Patch clamp recordings
- Intracellular recordings
- Application of ZD7288 and Cs(+) to rod photoreceptors
Main Results:
- ZD7288 inhibited I(h) in a concentration-dependent manner.
- ZD7288 selectively blocked I(h) without altering gating properties.
- Low concentrations of ZD7288 enhanced hyperpolarizing responses and delayed recovery, confirming I(h) involvement.
Conclusions:
- ZD7288 is a potent and selective inhibitor of I(h) in rod photoreceptors.
- I(h) plays a crucial role in accelerating response recovery from light-induced hyperpolarization.
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.