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 (K(IR)) also play a role. In this work we set to characterize the role of presynaptic K(IR) 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 Ba(2+) and Cs(+) reduced the PPR, suggesting that these channels are presynaptically located. Further pharmacological characterization showed that application of tertiapin-Q, a specific K(IR)3 channel family blocker, also induced a reduction of PPR, suggesting that K(IR)3 channels are present at corticostriatal terminals. In contrast, exposure to Lq2, a specific K(IR)1.1 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 K(IR)3 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 K(IR)3 channels.

The Histamine H3Receptor: Structure, Pharmacology, and Function

“…G bg subunits bind and activate G proteingated inwardly rectifying K 1 channels (GIRK) (Bünemann et al, 2001) and transfected hH 3 R 445 and hH 3 R 365 activate channels formed by the GIRK1 (Kir3.1) and GIRK4 (Kir3.4) subunits expressed in Xenopus oocytes (Sahlholm et al, 2012). GIRKs can inhibit synaptic transmission (Meneses et al, 2015), and activation of presynaptic GIRKs would thus represent an additional mechanism for H 3 Rs to modulate neurotransmitter release. Activation of GIRK channels by H 3 Rs has also been observed at the postsynaptic level in neurons producing melanin-concentrating hormone (MCH), where the effect was prevented by GDPbS, an inhibitor of G-protein signaling (Parks et al, 2014).…”

The role of Ca2+‐dependent K+‐ channels at the rat corticostriatal synapses revealed by paired pulse stimulation

“…The emerging picture of K + channels at the cortical synapse becomes richer and more complex every time. We have previously shown that glutamate release from cortical presynaptic terminals is influenced by the presence of several types of K + ‐channels, including K V 1, K V 3, and K IR 3 (Meneses et al, ). In this study, we have used BK‐specific and nonspecific K + ‐channels blockers to explore the presence and influence of presynaptic BK channels.…”

“…However, for some years now, it has become more evident that potassium channels are also present at presynaptic sites, where they contribute to fine‐tuning synaptic transmission. (Dodson & Forsythe, ; Meneses, Mateos, Islas, & Barral, , 2016; Rama, Zbili, & Debanne, ).…”

“…We have previously shown that synaptic transmission from cortical neurons to striatal medium spiny neurons (MNS) depends on both of Ca 2+ and K + ‐ channels (Barral, Galarraga, & Bargas, , 2000, 2001; Meneses et al, ). The presence of presynaptic potassium channels has been suggested earlier (Jiang & North, ; Miller, ; Quiang & Saggau, ; Tepper, Sawyer, Young, & Groves, ), but it has not been explored in detail.…”

“…The presence of presynaptic potassium channels has been suggested earlier (Jiang & North, ; Miller, ; Quiang & Saggau, ; Tepper, Sawyer, Young, & Groves, ), but it has not been explored in detail. Recently, we have shown that voltage‐gated potassium channels from K V 1 and K V 3 families as well as inward‐rectifying channels K IR 3 play a part on membrane excitability on the presynaptic side, tuning neurotransmitter release (Meneses et al, ). Here we set to explore if calcium‐dependent potassium channels (K Ca ) may also play a role at these synapses.…”