Abstract
1. The effects of diazoxide on ATP-K+ channel currents, recorded from the insulin-secreting cell line, CRI-G1, were studied using patch-clamp techniques. 2. Under current-clamp recording conditions diazoxide (0.6 mM), inhibited action potential activity and hyperpolarized CRI-G1 cells with a concomitant increase in membrane conductance. Recordings from voltage-clamped whole-cells and isolated patches indicate that activation of ATP-K+ channel currents underlie these effects. 3. Diazoxide elicited an activation of ATP-K+ channels which had been partially inhibited by ATP, on application to either surface of the plasma membrane, although it was more effective when applied directly to the cytoplasmic side. Activation of the ATP-K+ currents involves an increase in the single channel open-state probability and an apparent increase in the number of functional channels. 4. Activation was observed only when Mg-ATP was present in the cytoplasmic bathing solution. There was no activation of currents by diazoxide when ATP, in the absence of Mg2+ ions, or Mg-AMP-PNP was present to inhibit the ATP-K+ channels. 5. In the absence of ATP and Mg2+ ions in the cytoplasmic bathing solution, diazoxide (0.6 mM) produced an inhibition of ATP-K+ currents. 6. Cromakalim (BRL 34915) at 10 microM and 100 microM had no significant effects on ATP-K+ currents. 7. It is concluded that diazoxide-induced activation of ATP-K+ channel currents probably involves phosphorylation of the channel or some closely associated membrane protein.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ashcroft F. M. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988;11:97–118. doi: 10.1146/annurev.ne.11.030188.000525. [DOI] [PubMed] [Google Scholar]
- Ashcroft F. M., Ashcroft S. J., Harrison D. E. Properties of single potassium channels modulated by glucose in rat pancreatic beta-cells. J Physiol. 1988 Jun;400:501–527. doi: 10.1113/jphysiol.1988.sp017134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ashcroft F. M., Harrison D. E., Ashcroft S. J. Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells. 1984 Nov 29-Dec 5Nature. 312(5993):446–448. doi: 10.1038/312446a0. [DOI] [PubMed] [Google Scholar]
- Ashford M. L., Sturgess N. C., Cook D. L., Hales C. N. K-channels in an insulin-secreting cell line: effects of ATP and sulphonylureas. Adv Exp Med Biol. 1986;211:69–76. doi: 10.1007/978-1-4684-5314-0_6. [DOI] [PubMed] [Google Scholar]
- Ashford M. L., Sturgess N. C., Trout N. J., Gardner N. J., Hales C. N. Adenosine-5'-triphosphate-sensitive ion channels in neonatal rat cultured central neurones. Pflugers Arch. 1988 Aug;412(3):297–304. doi: 10.1007/BF00582512. [DOI] [PubMed] [Google Scholar]
- Carrington C. A., Rubery E. D., Pearson E. C., Hales C. N. Five new insulin-producing cell lines with differing secretory properties. J Endocrinol. 1986 May;109(2):193–200. doi: 10.1677/joe.0.1090193. [DOI] [PubMed] [Google Scholar]
- Cook D. L., Hales C. N. Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature. 1984 Sep 20;311(5983):271–273. doi: 10.1038/311271a0. [DOI] [PubMed] [Google Scholar]
- Cook D. L., Satin L. S., Ashford M. L., Hales C. N. ATP-sensitive K+ channels in pancreatic beta-cells. Spare-channel hypothesis. Diabetes. 1988 May;37(5):495–498. doi: 10.2337/diab.37.5.495. [DOI] [PubMed] [Google Scholar]
- Croghan P. C., Dawson C. M., Scott A. M., Bangham J. A. Contribution of isotope flux studies to understanding the mechanism of the beta-cell membrane. Adv Exp Med Biol. 1986;211:207–223. doi: 10.1007/978-1-4684-5314-0_19. [DOI] [PubMed] [Google Scholar]
- Dunne M. J., Illot M. C., Peterson O. H. Interaction of diazoxide, tolbutamide and ATP4- on nucleotide-dependent K+ channels in an insulin-secreting cell line. J Membr Biol. 1987;99(3):215–224. doi: 10.1007/BF01995702. [DOI] [PubMed] [Google Scholar]
- Findlay I. ATP-sensitive K+ channels in rat ventricular myocytes are blocked and inactivated by internal divalent cations. Pflugers Arch. 1987 Oct;410(3):313–320. doi: 10.1007/BF00580282. [DOI] [PubMed] [Google Scholar]
- Findlay I., Dunne M. J. ATP maintains ATP-inhibited K+ channels in an operational state. Pflugers Arch. 1986 Aug;407(2):238–240. doi: 10.1007/BF00580683. [DOI] [PubMed] [Google Scholar]
- Findlay I. The effects of magnesium upon adenosine triphosphate-sensitive potassium channels in a rat insulin-secreting cell line. J Physiol. 1987 Oct;391:611–629. doi: 10.1113/jphysiol.1987.sp016759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Hamilton T. C., Weir S. W., Weston A. H. Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol. 1986 May;88(1):103–111. doi: 10.1111/j.1476-5381.1986.tb09476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Misler S., Falke L. C., Gillis K., McDaniel M. L. A metabolite-regulated potassium channel in rat pancreatic B cells. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7119–7123. doi: 10.1073/pnas.83.18.7119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohno-Shosaku T., Zünkler B. J., Trube G. Dual effects of ATP on K+ currents of mouse pancreatic beta-cells. Pflugers Arch. 1987 Feb;408(2):133–138. doi: 10.1007/BF00581342. [DOI] [PubMed] [Google Scholar]
- Rorsman P., Trube G. Glucose dependent K+-channels in pancreatic beta-cells are regulated by intracellular ATP. Pflugers Arch. 1985 Dec;405(4):305–309. doi: 10.1007/BF00595682. [DOI] [PubMed] [Google Scholar]
- Sakmann B., Neher E. Patch clamp techniques for studying ionic channels in excitable membranes. Annu Rev Physiol. 1984;46:455–472. doi: 10.1146/annurev.ph.46.030184.002323. [DOI] [PubMed] [Google Scholar]
- Spruce A. E., Standen N. B., Stanfield P. R. Studies of the unitary properties of adenosine-5'-triphosphate-regulated potassium channels of frog skeletal muscle. J Physiol. 1987 Jan;382:213–236. doi: 10.1113/jphysiol.1987.sp016364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sturgess N. C., Ashford M. L., Cook D. L., Hales C. N. The sulphonylurea receptor may be an ATP-sensitive potassium channel. Lancet. 1985 Aug 31;2(8453):474–475. doi: 10.1016/s0140-6736(85)90403-9. [DOI] [PubMed] [Google Scholar]
- Sturgess N. C., Kozlowski R. Z., Carrington C. A., Hales C. N., Ashford M. L. Effects of sulphonylureas and diazoxide on insulin secretion and nucleotide-sensitive channels in an insulin-secreting cell line. Br J Pharmacol. 1988 Sep;95(1):83–94. doi: 10.1111/j.1476-5381.1988.tb16551.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trube G., Hescheler J. Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches. Pflugers Arch. 1984 Jun;401(2):178–184. doi: 10.1007/BF00583879. [DOI] [PubMed] [Google Scholar]
- Trube G., Rorsman P., Ohno-Shosaku T. Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic beta-cells. Pflugers Arch. 1986 Nov;407(5):493–499. doi: 10.1007/BF00657506. [DOI] [PubMed] [Google Scholar]
- Yount R. G. ATP analogs. Adv Enzymol Relat Areas Mol Biol. 1975;43:1–56. doi: 10.1002/9780470122884.ch1. [DOI] [PubMed] [Google Scholar]
- Zünkler B. J., Lenzen S., Männer K., Panten U., Trube G. Concentration-dependent effects of tolbutamide, meglitinide, glipizide, glibenclamide and diazoxide on ATP-regulated K+ currents in pancreatic B-cells. Naunyn Schmiedebergs Arch Pharmacol. 1988 Feb;337(2):225–230. doi: 10.1007/BF00169252. [DOI] [PubMed] [Google Scholar]