Year-end Sale % OFF 
Abstract
Vanadate is used as a tool to trap magnesium nucleotides in the catalytic site of ATPases. However, it has also been reported to activate ATP-sensitive potassium (K(ATP)) channels in the absence of nucleotides. K(ATP) channels comprise Kir6.2 and sulfonylurea receptor subunits (SUR1 in pancreatic beta cells, SUR2A in cardiac and skeletal muscle, and SUR2B in smooth muscle). We explored the effect of vanadate (2 mM), in the absence and presence of magnesium nucleotides, on different types of cloned K(ATP) channels expressed in Xenopus oocytes. Currents were recorded from inside-out patches. Vanadate inhibited Kir6.2/SUR1 currents by approximately 50% but rapidly activated Kir6.2/SUR2A ( approximately 4-fold) and Kir6. 2/SUR2B ( approximately 2-fold) currents. Mutations in SUR that abolish channel activation by magnesium nucleotides did not prevent the effects of vanadate. Studies with chimeric SUR indicate that the first six transmembrane domains account for the difference in both the kinetics and the vanadate response of Kir6.2/SUR1 and Kir6. 2/SUR2A. Boiling the vanadate solution, which removes the decavanadate polymers, largely abolished both stimulatory and inhibitory actions of vanadate. Our results demonstrate that decavanadate modulates K(ATP) channel activity via the SUR subunit, that this modulation varies with the type of SUR, that it differs from that produced by magnesium nucleotides, and that it involves transmembrane domains 1-6 of SUR.
Highlights
We further demonstrate that the interaction of vanadate with SUR is not mediated via the nucleotide-binding domains and that the first six transmembrane domains are required for activation of SUR2 by vanadate
This result indicates that the SUR subunit, rather than Kir6.2, is primarily responsible for the effects of vanadate on the wild-type KATP channel, a view that is supported by the disparate actions of vanadate on KATP channels containing different types of SUR subunit
The data presented in this paper clearly demonstrate that decavanadate interacts with the sulfonylurea receptor subunit of the KATP channel and that the effect of this interaction varies with the type of SUR subunit, being largely inhibitory for channels containing SUR1 and stimulatory for channels containing SUR2A or SUR2B
Summary
Peter Proks‡, Rebecca Ashfield, and Frances M. ATP-sensitive potassium (KATP) channels are found in a variety of tissues where they couple changes in cellular metabolism to electrical activity and potassium fluxes [1,2,3] Molecular cloning of these channels has revealed that they consist of two distinct types of subunit (a pore-forming subunit (Kir6.2) and a sulfonylurea receptor subunit (SUR1 in pancreatic beta cells, SUR2A in cardiac and skeletal muscle, and SUR2B in smooth muscle)) that associate in a 4:4 stoichiometry to form an octameric KATP channel. It has been reported to enhance the activity of KATP channels in skeletal muscle [24] and in ventricular myocytes [25], but it had no effect on the cloned KATP channel Kir6.2/ SUR1 in the presence of magnesium nucleotides [16] One explanation for these disparate findings is that different types of KATP channel exhibit different sensitivities to vanadate. This region determines the different kinetics of Kir6.2/SUR1 and Kir6.2/ SUR2 channels
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
