Effects of haloperidol on K(+) currents in acutely isolated rat retinal ganglion cells.
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.
Akamine
Takanobu
T
Department of Ophthalmology, Faculty of Medicine, Mie University, Tsu, Mie, Japan. akamine@momo.so-net.ne.jp
Nishimura
Yoshihiro
Y
Ito
Kunio
K
Uji
Yukitaka
Y
Yamamoto
Tetsuro
T
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
D018492:Dopamine Antagonists; D015221:Potassium Channels; D006220:Haloperidol; D011188:Potassium; D002118:Calcium