https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30562 h in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2, and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV⁺) or calretinin positive (CR⁺) inhibitory neurons. The effect of GBP on I_h was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100 μM) caused a hyperpolarizing shift in the voltage of half activation (V_1/2) thereby reducing the currents. Gabapentin had no impact on the V_1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1 channels. Gabapentin also caused a hyperpolarizing shift in the V_1/2 of I_h measured from HCN₄-expressing PV⁺ inhibitory neurons in the spinal dorsal horn. Gabapentin had minimal effect on I_h recorded from CR⁺ neurons. Consistent with this, immunohistochemical analysis revealed that the majority of CR⁺ inhibitory neurons do not express somatic HCN4 channels. In conclusion, GBP reduces HCN4 channel-mediated currents through a hyperpolarized shift in the V_1/2. The HCN channel subtype selectivity of GBP provides a unique tool for investigating HCN4 channel function in the central nervous system. The HCN4 channel is a candidate molecular target for the acute analgesic and anticonvulsant actions of GBP.]]> Wed 11 Apr 2018 16:01:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28096 Sat 24 Mar 2018 07:25:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24704 85% loss of 'pore' function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln-270His haplotype which confers dominant negative effects on P2X7 function and protection against MS. Modelling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory 'pore' function.]]> Sat 24 Mar 2018 07:10:52 AEDT ]]>