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Takanobu Akamine, Yoshihiro Nishimura, Kunio Ito, Yukitaka Uji, Tetsuro Yamamoto; Effects of Haloperidol on K+ Currents in Acutely Isolated Rat Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2002;43(4):1257-1261.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. 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 Ca2+-dependent K+ currents (KCa) were examined by whole-cell patch voltage clamp. Na+ currents were abolished by tetrodotoxin (1 μM; TTX). Voltage-gated IKs were isolated by Ca2+-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. KCa was identified by its response to TEA, charybdotoxin (CTX), and apamin. Haloperidol (0.01–100 μM) 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 [IC50] = 4.2 μM). The transient component of the voltage-gated IK was less sensitive to haloperidol. Haloperidol (10 nM) blocked the apamin-sensitive KCa but not the CTX-sensitive KCa.
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 KCa which modulates the firing rate of RGCs and may contribute to the alteration of PERG.
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