G-protein-coupled inward rectifier potassium channels involved in corticostriatal presynaptic modulation

ABSTRACT Presynaptic modulation has been associated mainly with calcium channels but recent data suggests that inward rectifier potassium channels (KIR) also play a role. In this work we set to characterize the role of presynaptic KIR channels in corticostriatal synaptic transmission. We elicited synaptic potentials in striatum by stimulating cortical areas and then determined the synaptic responses of corticostriatal synapsis by using paired pulse ratio (PPR) in the presence and absence of several potassium channel blockers. Unspecific potassium channels blockers Ba2+ and Cs+ reduced the PPR, suggesting that these channels are presynaptically located. Further pharmacological characterization showed that application of tertiapin‐Q, a specific KIR3 channel family blocker, also induced a reduction of PPR, suggesting that KIR3 channels are present at corticostriatal terminals. In contrast, exposure to Lq2, a specific KIR1.1 inward rectifier potassium channel, did not induce any change in PPR suggesting the absence of these channels in the presynaptic corticostriatal terminals. Our results indicate that KIR3 channels are functionally expressed at the corticostriatal synapses, since blockage of these channels result in PPR decrease. Our results also help to explain how synaptic activity may become sensitive to extracellular signals mediated by G‐protein coupled receptors. A vast repertoire of receptors may influence neurotransmitter release in an indirect manner through regulation of KIR3 channels. Synapse 69:446–452, 2015. 2015 Wiley Periodicals, Inc. Specific KIR3.X channel blocker, tertiapin‐Q, decrease extracellular recording paired pulse ratio, indicating inward rectifier potassium channels presynaptic regulation at the corticostriatal synapse. These data are consistent with presynaptic GIRK channels in proximity to the active zone, suggesting a possible role in regulating neurotransmitter release at the corticostriatal synapse.