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 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.
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 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.