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

摘要: Abstract Recently it has been reported that “If channel blockers”, which block the hyperpolarization-activated inward current (If) in heart sino atrial node cells, also (Ih) other tissues. Here we compared effects of one these agents, ZD7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride], with those Cs+ on Ih amphibian rod photoreceptors using patch clamp and intracellular recordings. strongly inhibited newt a concentration-dependent manner (1–100 μM). exerted blocking action conductance no alteration its gating properties, was not use-dependent. At concentrations as low 1 μM, markedly enhanced hyperpolarizing membrane responses frog to bright light delayed response recovery, indicating is highly selective for Ih. The apparent effect drug slow onset irreversible, suggesting act at cytosolic site channel. These observations confirm involvement accelerating recovery process from deep hyperpolarization induced by cells.