Nucleotide modulation of pinacidil stimulation of the cloned K(ATP) channel Kir6.2/SUR2A. by Gribble, F, Reimann, F, Ashfield, R, Ashcroft, F

“…To determine the reason for this anomaly, we examined the functional interactions between pinacidil (or P1075) and nucleotides by expressing cloned Kir6. 2/SUR2A channels in Xenopus laevis oocytes. Both pinacidil and P1075 activated macroscopic Kir6.2/SUR2A currents in the absence of added nucleotide, but the presence of intracellular ATP or ADP slowed the off-rate of the response. …”

Relapsing diabetes can result from moderately activating mutations in KCNJ11. by Gloyn, A, Reimann, F, Girard, C, Edghill, E, Proks, P, Pearson, E, Temple, I, Mackay, D, Shield, J, Freedenberg, D, Noyes, K, Ellard, S, Ashcroft, F, Gribble, F, Hattersley, A

“…Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. …”

Characterisation of new KATP-channel mutations associated with congenital hyperinsulinism in the Finnish population. by Reimann, F, Huopio, H, Dabrowski, M, Proks, P, Gribble, F, Laakso, M, Otonkoski, T, Ashcroft, F

“…METHODS: Wild type or mutant Kir6.2 and SUR1 subunits were coexpressed in Xenopus oocytes. The functional properties of the channels were examined by measuring currents in intact oocytes or giant inside-out membrane patches. …”

The role of lysine 185 in the kir6.2 subunit of the ATP-sensitive channel in channel inhibition by ATP. by Reimann, F, Ryder, T, Tucker, S, Ashcroft, F

“…To determine if K185 interacts directly with ATP, we made a range of mutations at this position, and examined the effect on the channel ATP sensitivity by recording macroscopic currents in membrane patches excised from Xenopus oocytes expressing wild-type or mutant Kir6.2DeltaC26. 4. …”

Analysis of the differential modulation of sulphonylurea block of beta-cell and cardiac ATP-sensitive K+ (K(ATP)) channels by Mg-nucleotides. by Reimann, F, Dabrowski, M, Jones, P, Gribble, F, Ashcroft, F

“…We examined the molecular basis of the different response of channels containing SUR1 and SUR2A, by recording currents from inside-out patches excised from Xenopus oocytes heterologously expressing wild-type or chimeric channels. …”

Structural basis for the interference between nicorandil and sulfonylurea action. by Reimann, F, Ashcroft, F, Gribble, F

“…We expressed recombinant K(ATP) channels in Xenopus oocytes and measured the effects of drugs and nucleotides by recording macroscopic currents in excised membrane patches. …”

Effects of mitiglinide (S 21403) on Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.2/SUR2B types of ATP-sensitive potassium channel. by Reimann, F, Proks, P, Ashcroft, F

“…Kir6.2 was coexpressed with SUR1, SUR2A or SUR2B in Xenopus oocytes and macroscopic currents were recorded in giant inside-out membrane patches. …”

Differential response of K(ATP) channels containing SUR2A or SUR2B subunits to nucleotides and pinacidil. by Reimann, F, Gribble, F, Ashcroft, F

“…We explored the basis for this difference by expressing Kir6.2/SUR2A and Kir6.2/SUR2B currents in Xenopus laevis oocytes. Kir6.2/SUR2B but not Kir6.2/SUR2A currents were activated by the Mg-nucleoside triphosphates MgATP and MgGTP, whereas both channel types responded to the diphosphates MgADP and MgGDP. …”

Involvement of the n-terminus of Kir6.2 in coupling to the sulphonylurea receptor. by Reimann, F, Tucker, S, Proks, P, Ashcroft, F

“…We examined the effect of N-terminal deletions of Kir6.2 on the channel open probability, ATP sensitivity and sulphonylurea sensitivity by recording macroscopic currents in membrane patches excised from Xenopus oocytes expressing wild-type or mutant Kir6.2/SUR1. 3. …”