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. 1989 Dec;419:297–320. doi: 10.1113/jphysiol.1989.sp017874

The Mg2+ block and intrinsic gating underlying inward rectification of the K+ current in guinea-pig cardiac myocytes.

K Ishihara 1, T Mitsuiye 1, A Noma 1, M Takano 1
PMCID: PMC1190009  PMID: 2621633

Abstract

1. The blockade by Mg2+ and intrinsic gating of the channel, which underlie the rectification of the inward rectifier K+ current, was investigated using the oil-gap voltage clamp method in isolated guinea-pig ventricular cells. 2. The inward rectifier K+ current was isolated by subtracting trans-gap currents recorded at an extracellular K+ concentration ([K+]o) of 0 mM from those obtained at 14 mM [K+]o in the presence of a given concentration of intracellular Mg2+ ([Mg2+]i). The reversal potential (V0) of the difference current was near the equilibrium potential for K+ (EK). 3. On repolarization across EK, the inward rectifier K+ current showed a rapid exponential increase. The time constant decreased with increasing hyperpolarization, but it was independent of both [Mg2+]i and the preceding depolarization. 4. When the pre-pulse potential was made progressively positive between V0-20 and V0 + 30 mV, the amplitude of the time-dependent component became larger and the preceding current jump decreased at any [Mg2+]i. With pre-pulses more positive than V0 + 40 mV, the time-dependent component started from almost the zero current level at 2 microM [Mg2+]i. At higher [Mg2+]i (350, 500 and 3000 microM), however, the time-dependent component became smaller as the pre-pulse potential was made more positive than V0 + 40 mV. 5. When the membrane was depolarized from a potential of full activation at 2 microM [Mg2+]i, the initial jump in the outward current was ohmic and was followed by an exponential decay. The time-dependent component of the inward current, recorded on repolarization after increasing durations of the preceding depolarization, developed as the outward current decayed. The time constants of both processes were in good agreement. 6. At 500 microM [Mg2+]i, the outward current on depolarization was instantaneously rectified. The time-dependent component recorded on repolarization developed with prolongation of the pre-pulse with a time course slower than at 2 microM [Mg2+]i. The envelope time course became slower as the potential of the depolarization became more positive. 7. Lowering the temperature from 23 to 15 degrees C slowed the time-dependent current with an apparent Q10 of about 3.5 at V0. 8. Based on the experimental data, kinetic parameters were estimated for a model of Mg2+ block, which well simulated the inward-going rectification of the K+ current. 9. It is concluded that the instantaneous inward rectification on depolarization is due to the Mg2+ block at physiological [Mg2+]i.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Biermans G., Vereecke J., Carmeliet E. The mechanism of the inactivation of the inward-rectifying K current during hyperpolarizing steps in guinea-pig ventricular myocytes. Pflugers Arch. 1987 Dec;410(6):604–613. doi: 10.1007/BF00581320. [DOI] [PubMed] [Google Scholar]
  2. Blatter L. A., McGuigan J. A. Free intracellular magnesium concentration in ferret ventricular muscle measured with ion selective micro-electrodes. Q J Exp Physiol. 1986 Jul;71(3):467–473. doi: 10.1113/expphysiol.1986.sp003005. [DOI] [PubMed] [Google Scholar]
  3. Coraboeuf E., Carmeliet E. Existence of two transient outward currents in sheep cardiac Purkinje fibers. Pflugers Arch. 1982 Feb;392(4):352–359. doi: 10.1007/BF00581631. [DOI] [PubMed] [Google Scholar]
  4. DeCoursey T. E., Dempster J., Hutter O. F. Inward rectifier current noise in frog skeletal muscle. J Physiol. 1984 Apr;349:299–327. doi: 10.1113/jphysiol.1984.sp015158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FRANKENHAEUSER B., MOORE L. E. THE EFFECT OF TEMPERATURE ON THE SODIUM AND POTASSIUM PERMEABILITY CHANGES IN MYELINATED NERVE FIBRES OF XENOPUS LAEVIS. J Physiol. 1963 Nov;169:431–437. doi: 10.1113/jphysiol.1963.sp007269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fabiato A., Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 1979;75(5):463–505. [PubMed] [Google Scholar]
  7. Gupta R. K., Gupta P., Moore R. D. NMR studies of intracellular metal ions in intact cells and tissues. Annu Rev Biophys Bioeng. 1984;13:221–246. doi: 10.1146/annurev.bb.13.060184.001253. [DOI] [PubMed] [Google Scholar]
  8. Hagiwara S., Miyazaki S., Rosenthal N. P. Potassium current and the effect of cesium on this current during anomalous rectification of the egg cell membrane of a starfish. J Gen Physiol. 1976 Jun;67(6):621–638. doi: 10.1085/jgp.67.6.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hagiwara S., Yoshii M. Effect of temperature on the anomalous rectification of the membrane of the egg of the starfish, Mediaster aequalis. J Physiol. 1980 Oct;307:517–527. doi: 10.1113/jphysiol.1980.sp013451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hagiwara S., Yoshii M. Effects of internal potassium and sodium on the anomalous rectification of the starfish egg as examined by internal perfusion. J Physiol. 1979 Jul;292:251–265. doi: 10.1113/jphysiol.1979.sp012849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hess P., Metzger P., Weingart R. Free magnesium in sheep, ferret and frog striated muscle at rest measured with ion-selective micro-electrodes. J Physiol. 1982 Dec;333:173–188. doi: 10.1113/jphysiol.1982.sp014447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hestrin S. The interaction of potassium with the activation of anomalous rectification in frog muscle membrane. J Physiol. 1981 Aug;317:497–508. doi: 10.1113/jphysiol.1981.sp013839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hiraoka M., Kawano S. Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes. J Physiol. 1989 Mar;410:187–212. doi: 10.1113/jphysiol.1989.sp017528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Horie M., Irisawa H. Dual effects of intracellular magnesium on muscarinic potassium channel current in single guinea-pig atrial cells. J Physiol. 1989 Jan;408:313–332. doi: 10.1113/jphysiol.1989.sp017461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Horie M., Irisawa H. Rectification of muscarinic K+ current by magnesium ion in guinea pig atrial cells. Am J Physiol. 1987 Jul;253(1 Pt 2):H210–H214. doi: 10.1152/ajpheart.1987.253.1.H210. [DOI] [PubMed] [Google Scholar]
  17. Imoto Y., Ehara T., Goto M. Calcium channel currents in isolated guinea-pig ventricular cells superfused with Ca-free EGTA solution. Jpn J Physiol. 1985;35(6):917–932. doi: 10.2170/jjphysiol.35.917. [DOI] [PubMed] [Google Scholar]
  18. Isenberg G. Cardiac Purkinje fibers: cesium as a tool to block inward rectifying potassium currents. Pflugers Arch. 1976 Sep 30;365(2-3):99–106. doi: 10.1007/BF01067006. [DOI] [PubMed] [Google Scholar]
  19. Isenberg G., Klockner U. Calcium tolerant ventricular myocytes prepared by preincubation in a "KB medium". Pflugers Arch. 1982 Oct;395(1):6–18. doi: 10.1007/BF00584963. [DOI] [PubMed] [Google Scholar]
  20. Josephson I. R., Sanchez-Chapula J., Brown A. M. Early outward current in rat single ventricular cells. Circ Res. 1984 Feb;54(2):157–162. doi: 10.1161/01.res.54.2.157. [DOI] [PubMed] [Google Scholar]
  21. Kurachi Y. Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guinea-pig heart. J Physiol. 1985 Sep;366:365–385. doi: 10.1113/jphysiol.1985.sp015803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Leech C. A., Stanfield P. R. Inward rectification in frog skeletal muscle fibres and its dependence on membrane potential and external potassium. J Physiol. 1981;319:295–309. doi: 10.1113/jphysiol.1981.sp013909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Matsuda H., Noma A. Isolation of calcium current and its sensitivity to monovalent cations in dialysed ventricular cells of guinea-pig. J Physiol. 1984 Dec;357:553–573. doi: 10.1113/jphysiol.1984.sp015517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Matsuda H. Open-state substructure of inwardly rectifying potassium channels revealed by magnesium block in guinea-pig heart cells. J Physiol. 1988 Mar;397:237–258. doi: 10.1113/jphysiol.1988.sp016998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Matsuda H., Saigusa A., Irisawa H. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature. 1987 Jan 8;325(7000):156–159. doi: 10.1038/325156a0. [DOI] [PubMed] [Google Scholar]
  26. Mitsuiye T., Noma A. A new oil-gap method for internal perfusion and voltage clamp of single cardiac cells. Pflugers Arch. 1987 Sep;410(1-2):7–14. doi: 10.1007/BF00581889. [DOI] [PubMed] [Google Scholar]
  27. Nakayama T., Irisawa H. Transient outward current carried by potassium and sodium in quiescent atrioventricular node cells of rabbits. Circ Res. 1985 Jul;57(1):65–73. doi: 10.1161/01.res.57.1.65. [DOI] [PubMed] [Google Scholar]
  28. Ohmori H. Inactivation kinetics and steady-state current noise in the anomalous rectifier of tunicate egg cell membranes. J Physiol. 1978 Aug;281:77–99. doi: 10.1113/jphysiol.1978.sp012410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Powell T., Terrar D. A., Twist V. W. Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol. 1980 May;302:131–153. doi: 10.1113/jphysiol.1980.sp013234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Saigusa A., Matsuda H. Outward currents through the inwardly rectifying potassium channel of guinea-pig ventricular cells. Jpn J Physiol. 1988;38(1):77–91. doi: 10.2170/jjphysiol.38.77. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Sakmann B., Trube G. Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol. 1984 Feb;347:659–683. doi: 10.1113/jphysiol.1984.sp015089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vandenberg C. A. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2560–2564. doi: 10.1073/pnas.84.8.2560. [DOI] [PMC free article] [PubMed] [Google Scholar]

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