Abstract
K+ currents were recorded from ATP-sensitive channels in inside-out membrane patches excised from isolated rat ventricular myocytes. ATP-sensitive K+ channel inhibition could be evoked by ATP in the absence of magnesium where most ATP would be present as the free acid ATP4−. Channel inhibition was enhanced when the same total concentration of ATP was applied in the presence of magnesium, where most ATP would be bound as ATP·Mg. Dose-response relationships for ATP-sensitive K+ channel inhibition evoked by ATP had a Hill coefficient of 2 andK i of 17 and 30 μM for ATP in the presence and absence of magnesium respectively. This was the obverse of the expected results if ATP4− were to be the sole form of ATP to effect channel closure. ATP-sensitive K+ channel inhibition evoked by ATPγS, AMP-PNP and AMP-PCP was also enhanced in the presence of magnesium. It is concluded that the ATP-sensitive K+ channel of rat ventricular myocytes binds and is closed by both the free-acid and divalent-cationbound forms of ATP.
Similar content being viewed by others
References
Ashcroft FM, Kakei M (1987) Effects of internal Mg2+ on ATP-sensitive K-channels in isolated rat pancreatic B-cells. J Physiol 390:72P
Cockcroft S, Gomperts BD (1980) The ATP4− receptor of rat mast cells. Biochem J 188:789–798
Cook DL, Hales CN (1984) Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature 311:271–273
Dunne MJ, Petersen OH (1986) Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin-secreting cell line. FEBS Lett 208:59–62
Dunne MJ, Illot MC, Petersen OH (1987) Interaction of diazoxide, tolbutamide and ATP4− on nucleotide-dependent K+ channels in an insulin-secreting cell line. J Membr Biol 99:215–224
Findlay I (1987a) The effects of magnesium upon adenosine triphosphate-sensitive potassium channels in a rat insulin-secreting cell line. J Physiol 391:611–629
Findlay I (1987b) ATP-sensitive K+ channels in rat ventricular myocytes are blocked and inactivated by internal divalent cations. Pflügers Arch 410:313–320
Flatman PW (1984) Magnesium transport across cell membranes. J Membr Biol 80:1–14
Gordon JL (1986) Extracellular ATP: effects, sources and fate. Biochem J 233:309–319
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100
Martell AE, Smith RM (1974) Critical stability constants, vol 1, Amino acids. Plenum Press, New York
Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305:147–148
Ohno-Shosaku T, Zunkler BJ, Trube G (1987) Dual effects of ATP on K+ currents of mouse pancreatic b-cells. Pflügers Arch 408:133–138
Ribalet B, Ciani S (1987) Regulation by cell metabolism and adenine nucleotides of a K channel in insulin-secreting B cells (RINm5F). Proc Natl Acad Sci USA 84:1721–1725
Sillén LG, Martell AE (1964) Stability constants of metal-ion complexes. Special Publication no. 17. The Chemical Society, London
Stanfield PR (1987) Nucleotides such as ATP may control the activity of ion channels. Trends Neurosci 10:335–339
Trube G, Hescheler J (1984) Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches. Pflügers Arch 401:178–184
Yount RG (1975) ATP analogs. Adv Enzymol 43:1–56
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Findlay, I. ATP4− and ATP·Mg inhibit the ATP-sensitive K+ channel of rat ventricular myocytes. Pflugers Arch. 412, 37–41 (1988). https://doi.org/10.1007/BF00583729
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00583729