Niflumic acid reduces the hyperpolarization-activated current (I(h)) in rod photoreceptor cells.
We examined the effects of niflumic acid (NFA), a chloride channel blocker, on the hyperpolarization-activated current (I(h)) in newt rod photoreceptors. At 100 microM, NFA delayed the activation of I(h) induced by hyperpolarizing voltage pulses to -83 mV from a holding potential of -43 mV, and reduced the steady-state current. However, reduction by NFA was weakened when I(h) was activated by hyperpolarizing steps to -123 mV, suggesting that these effects were voltage-dependent. The suppressive effects of NFA on I(h) were accompanied by a negative shift in activation voltage. NFA also delayed the relaxation of I(h) tail currents, showing that this drug also inhibited deactivation of the current. The reversal potential and the fully activated conductance were not affected. These observations suggest that NFA reduces I(h) by modifying the gating kinetics of the underlying channels. The suppressive actions of NFA remained when intracellular Ca2+ was strongly chelated, and the failure of suppression by NFA in inside-out patches suggests that the agent may act on the I(h) channel from the extracellular side. These results, obtained in rod photoreceptors, are consistent with similar effects of NFA on I(f) in cardiac myocytes, suggesting that both currents share similar pharmacological properties.
Satoh
T O
TO
Supermolecular Division, Electrotechnical Laboratory, Tsukuba, 305-8568, Ibaraki, Japan.
Yamada
M
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D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009544:Niflumic Acid / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012455:Salamandridae; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D016861:Cyclooxygenase Inhibitors; D007473:Ion Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009544:Niflumic Acid; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid