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. 1990 Apr;423:91–110. doi: 10.1113/jphysiol.1990.sp018013

The regulation of ATP-sensitive K+ channel activity in intact and permeabilized rat ventricular myocytes.

C G Nichols 1, W J Lederer 1
PMCID: PMC1189748  PMID: 2388163

Abstract

1. In isolated rat heart ventricular myocytes exposed to 2 mM-cyanide in the presence of 10 mM-2-deoxyglucose (complete metabolic blockade), there is a time-dependent increase in ATP-sensitive potassium (KATP) channel activity. The increase in KATP channel activity accompanies the decline of twitch amplitude. Channel activation and decline of the twitch amplitude precede the development of a 'rigor' contracture. 2. We measured KATP channel activity in permeabilized cells using the open-cell attached (O-C-A) patch configuration (by establishing a cell-attached patch and then permeabilizing the cell by exposure to saponin). The apparent ATP dependence of KATP channel activity could be described by a sigmoid curve with ki, ATP (ATP concentration required for half-maximum inhibition of channel activity) = 122 microM and H (Hill coefficient) = 1.225. 3. In the O-C-A patch configuration, 10 mM-creatine phosphate (CrP) decreased the apparent ki, ATP from 122 microM to about 10 microM, and the maximal activity (in zero ATP) was decreased to about 30% of the maximal activity in the absence of CrP. 4. In isolated inside-out (I-O) patches, ATP inhibited KATP channel activity at much lower [ATP] than in the O-C-A patch configuration (ki, ATP = 25 microM, H = 2). CrP was without effect on I-O patches. 5. These results are consistent with the hypothesis that the difference in the ATP dependence of KATP channel activity in the O-C-A and I-O patch configurations arises because of ATP consumption in the O-C-A patch configuration. The results suggest that hydrolysis of ATP to ADP by endogenous ATPases leads to the development of gradients of [ATP] and [ADP] between the bath and the 'inside' of the open cell. By re-phosphorylating ADP, CrP is able to dissipate these gradients, revealing the 'true' ATP dependence of channel activity, which is the same as that in the I-O patch configuration. 6. In order to estimate the contribution of KATP channel activity to the rat cardiac action potential at different [ATP] we have made the following measurements. Using electrodes of resistance 2-8 M omega the density of KATP channels was 10.3 +/- 0.1 channels per patch (n = 162).(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Allen D. G., Morris P. G., Orchard C. H., Pirolo J. S. A nuclear magnetic resonance study of metabolism in the ferret heart during hypoxia and inhibition of glycolysis. J Physiol. 1985 Apr;361:185–204. doi: 10.1113/jphysiol.1985.sp015640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen D. G., Orchard C. H. Myocardial contractile function during ischemia and hypoxia. Circ Res. 1987 Feb;60(2):153–168. doi: 10.1161/01.res.60.2.153. [DOI] [PubMed] [Google Scholar]
  3. Baumgarten C. M., Cohen C. J., McDonald T. F. Heterogeneity of intracellular potassium activity and membrane potential in hypoxic guinea pig ventricle. Circ Res. 1981 Nov;49(5):1181–1189. doi: 10.1161/01.res.49.5.1181. [DOI] [PubMed] [Google Scholar]
  4. Belles B., Hescheler J., Trube G. Changes of membrane currents in cardiac cells induced by long whole-cell recordings and tolbutamide. Pflugers Arch. 1987 Aug;409(6):582–588. doi: 10.1007/BF00584657. [DOI] [PubMed] [Google Scholar]
  5. Bessman S. P., Carpenter C. L. The creatine-creatine phosphate energy shuttle. Annu Rev Biochem. 1985;54:831–862. doi: 10.1146/annurev.bi.54.070185.004151. [DOI] [PubMed] [Google Scholar]
  6. Cannell M. B., Lederer W. J. A novel experimental chamber for single-cell voltage-clamp and patch-clamp applications with low electrical noise and excellent temperature and flow control. Pflugers Arch. 1986 May;406(5):536–539. doi: 10.1007/BF00583378. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Cooke R., Pate E. The effects of ADP and phosphate on the contraction of muscle fibers. Biophys J. 1985 Nov;48(5):789–798. doi: 10.1016/S0006-3495(85)83837-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DiFrancesco D., Noble D. A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos Trans R Soc Lond B Biol Sci. 1985 Jan 10;307(1133):353–398. doi: 10.1098/rstb.1985.0001. [DOI] [PubMed] [Google Scholar]
  10. Elliott A. C., Smith G. L., Allen D. G. Simultaneous measurements of action potential duration and intracellular ATP in isolated ferret hearts exposed to cyanide. Circ Res. 1989 Mar;64(3):583–591. doi: 10.1161/01.res.64.3.583. [DOI] [PubMed] [Google Scholar]
  11. Fabiato A., Fabiato F. Effects of magnesium on contractile activation of skinned cardiac cells. J Physiol. 1975 Aug;249(3):497–517. doi: 10.1113/jphysiol.1975.sp011027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Findlay I. ATP4- and ATP.Mg inhibit the ATP-sensitive K+ channel of rat ventricular myocytes. Pflugers Arch. 1988 Jul;412(1-2):37–41. doi: 10.1007/BF00583729. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fosset M., De Weille J. R., Green R. D., Schmid-Antomarchi H., Lazdunski M. Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels. J Biol Chem. 1988 Jun 15;263(17):7933–7936. [PubMed] [Google Scholar]
  16. Gibbs C. L. Cardiac energetics. Physiol Rev. 1978 Jan;58(1):174–254. doi: 10.1152/physrev.1978.58.1.174. [DOI] [PubMed] [Google Scholar]
  17. Hearse D. J. Oxygen deprivation and early myocardial contractile failure: a reassessment of the possible role of adenosine triphosphate. Am J Cardiol. 1979 Nov;44(6):1115–1121. doi: 10.1016/0002-9149(79)90177-2. [DOI] [PubMed] [Google Scholar]
  18. Horie M., Irisawa H., Noma A. Voltage-dependent magnesium block of adenosine-triphosphate-sensitive potassium channel in guinea-pig ventricular cells. J Physiol. 1987 Jun;387:251–272. doi: 10.1113/jphysiol.1987.sp016572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jones D. P. Intracellular diffusion gradients of O2 and ATP. Am J Physiol. 1986 May;250(5 Pt 1):C663–C675. doi: 10.1152/ajpcell.1986.250.5.C663. [DOI] [PubMed] [Google Scholar]
  20. Kakei M., Noma A., Shibasaki T. Properties of adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol. 1985 Jun;363:441–462. doi: 10.1113/jphysiol.1985.sp015721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lederer W. J., Nichols C. G. Nucleotide modulation of the activity of rat heart ATP-sensitive K+ channels in isolated membrane patches. J Physiol. 1989 Dec;419:193–211. doi: 10.1113/jphysiol.1989.sp017869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lederer W. J., Nichols C. G., Smith G. L. The mechanism of early contractile failure of isolated rat ventricular myocytes subjected to complete metabolic inhibition. J Physiol. 1989 Jun;413:329–349. doi: 10.1113/jphysiol.1989.sp017657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mercer R. W., Dunham P. B. Membrane-bound ATP fuels the Na/K pump. Studies on membrane-bound glycolytic enzymes on inside-out vesicles from human red cell membranes. J Gen Physiol. 1981 Nov;78(5):547–568. doi: 10.1085/jgp.78.5.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Meyer R. A., Sweeney H. L., Kushmerick M. J. A simple analysis of the "phosphocreatine shuttle". Am J Physiol. 1984 May;246(5 Pt 1):C365–C377. doi: 10.1152/ajpcell.1984.246.5.C365. [DOI] [PubMed] [Google Scholar]
  25. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8;305(5930):147–148. doi: 10.1038/305147a0. [DOI] [PubMed] [Google Scholar]
  26. Noma A., Shibasaki T. Membrane current through adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol. 1985 Jun;363:463–480. doi: 10.1113/jphysiol.1985.sp015722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Paul R. J. Functional compartmentalization of oxidative and glycolytic metabolism in vascular smooth muscle. Am J Physiol. 1983 May;244(5):C399–C409. doi: 10.1152/ajpcell.1983.244.5.C399. [DOI] [PubMed] [Google Scholar]
  29. Qin D. Y., Noma A. A new oil-gate concentration jump technique applied to inside-out patch-clamp recording. Am J Physiol. 1988 Oct;255(4 Pt 2):H980–H984. doi: 10.1152/ajpheart.1988.255.4.H980. [DOI] [PubMed] [Google Scholar]
  30. Sakmann B., Trube G. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol. 1984 Feb;347:641–657. doi: 10.1113/jphysiol.1984.sp015088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Steadman B. W., Moore K. B., Spitzer K. W., Bridge J. H. A video system for measuring motion in contracting heart cells. IEEE Trans Biomed Eng. 1988 Apr;35(4):264–272. doi: 10.1109/10.1375. [DOI] [PubMed] [Google Scholar]
  32. Stern M. D., Silverman H. S., Houser S. R., Josephson R. A., Capogrossi M. C., Nichols C. G., Lederer W. J., Lakatta E. G. Anoxic contractile failure in rat heart myocytes is caused by failure of intracellular calcium release due to alteration of the action potential. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6954–6958. doi: 10.1073/pnas.85.18.6954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Ventura-Clapier R., Mekhfi H., Vassort G. Role of creatine kinase in force development in chemically skinned rat cardiac muscle. J Gen Physiol. 1987 May;89(5):815–837. doi: 10.1085/jgp.89.5.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. WILLIAMSON J. R. GLYCOLYTIC CONTROL MECHANISMS. I. INHIBITION OF GLYCOLYSIS BY ACETATE AND PYRUVATE IN THE ISOLATED, PERFUSED RAT HEART. J Biol Chem. 1965 Jun;240:2308–2321. [PubMed] [Google Scholar]
  36. Weiss J. N., Lamp S. T. Glycolysis preferentially inhibits ATP-sensitive K+ channels in isolated guinea pig cardiac myocytes. Science. 1987 Oct 2;238(4823):67–69. doi: 10.1126/science.2443972. [DOI] [PubMed] [Google Scholar]

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