title: Effects of haloperidol on K(+) currents in acutely isolated rat retinal ganglion cells.
abstract: OBJECTIVE
  Effects of haloperidol on K(+) currents (IKs) of rat retinal ganglion cells (RGCs) were examined, with the hypothesis that its alteration of IKs explains alterations in the pattern electroretinogram (PERG).
  
  
  METHODS
  Fast blue was injected into superior colliculi of rats (3-8 days old) to identify RGCs under epifluorescence illumination after retrograde transport to retinas. Retinas were dissected, treated enzymatically, and dissociated with trituration. Effects of haloperidol on membrane currents at -70 mV, voltage-dependent IK, and Ca(2+)-dependent K(+) currents (K(Ca)) were examined by whole-cell patch voltage clamp. Na(+) currents were abolished by tetrodotoxin (1 microM; TTX). Voltage-gated IKs were isolated by Ca(2+)-free perfusate. Persistent and transient components of the voltage-sensitive IKs were isolated by prepulses, and sensitivity of each component to tetraethylammonium (TEA, 20 mM) and 4-aminopyridine (5 mM) was tested. K(Ca) was identified by its response to TEA, charybdotoxin (CTX), and apamin. Haloperidol (0.01-100 microM) was instilled into the perfusate dissolved in dimethyl sulfoxide (DMSO).
  
  
  RESULTS
  Currents recorded at -70 mV were not affected by haloperidol, whereas the persistent component of the voltage-dependent IK was reversibly reduced by haloperidol, with a dose dependence fitted with the Hill equation (median inhibitory concentration [IC(50)] = 4.2 microM). The transient component of the voltage-gated IK was less sensitive to haloperidol. Haloperidol (10 nM) blocked the apamin-sensitive K(Ca) but not the CTX-sensitive K(Ca).
  
  
  CONCLUSIONS
  Haloperidol reduced voltage-dependent IKs in RGCs, but at a higher concentration than that needed to antagonize dopamine receptors. Haloperidol (10 nM) blocked the apamin-sensitive K(Ca) which modulates the firing rate of RGCs and may contribute to the alteration of PERG.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Mie University, Tsu, Mie, Japan. akamine@momo.so-net.ne.jp
authors.forename: Takanobu
authors.initials: T
authors.lastname: Akamine
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Kunio
authors.initials: K
authors.lastname: Ito
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Uji
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018492:Dopamine Antagonists; D015221:Potassium Channels; D006220:Haloperidol; D011188:Potassium; D002118:Calcium