Add time:09/10/2019         Source:sciencedirect.com

Recently it has been reported that “If channel blockers”, which block the hyperpolarization-activated inward current (If) in heart sino atrial node cells, also block the hyperpolarization-activated inward current (Ih) in other tissues. Here we compared the effects of one of these agents, ZD7288 (cas 133059-99-1) [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride], with those of Cs+ on Ih in amphibian rod photoreceptors using patch clamp and intracellular recordings. ZD7288 strongly inhibited Ih in newt rod photoreceptors in a concentration-dependent manner (1–100 μM). ZD7288 exerted a blocking action on the conductance of Ih with no alteration of its gating properties, and the blocking action of Ih 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 Ih. The apparent effect of the drug was slow in onset and irreversible, suggesting that ZD7288 act at a cytosolic site on the Ih channel. These observations also confirm the involvement of Ih in accelerating the response recovery process from deep membrane hyperpolarization induced by bright light in rod cells.

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