The Journal of Membrane Biology

, Volume 122, Issue 1, pp 33–42 | Cite as

Permeance of Cs+ and Rb+ through the inwardly rectifying K+ channel in guinea pig ventricular myocytes

  • Raman L. Mitra
  • Martin Morad


Inward currents carried by external Cs, Rb, NH4 and K through theIK1 channel were studied using a whole-cell voltage clamp technique. Cs, NH4, and Rb currents could be recorded negative to −40 mV following depolarizing prepulses (≥0 mV and 200–1000 msec in duration). The current activation displayed an instantaneous component followed by a monoexponential increase (τα) to a peak amplitude. Subsequent inactivation was fit by a single exponential, τ. With hyperpolarization, τα and τ decreasede-fold per 36 and 25 mV, respectively. In Ca-free external solutions (pipette [Mg]≈0.3mm), inactivation was absent, consistent with the hypothesis that inactivation represents time- and voltage-dependent block of Cs, NH4, and Rb currents by external Ca. The inactivation and degree of steady-state block was greatest when Cs was the charge carrier, followed by NH4, and then Rb. K currents, however, did not inactivate in the presence of Ca. Na and Li did not carry any significant current within the resolution of our recordings. Comparison ofpeak inward current ratios (Ix/IK) as an index of permeability revealed a higher permeance of Cs (0.15), NH4 (0.30), and Rb (0.51) relative to K (1.0) than that obtained by comparing thesteady-state current ratios (Cs∶NH4∶Rb∶K≈0.01∶0.06∶0.21∶1.0). At any given potential, τα was smaller the more permeant the cation. In the absence of depolarizing prepulses, the amplitude of τα was reduced. Divalent-free solutions did not significantly affect activatio in the presence of 0.3mm pipette [Mg]. When pipette [Mg] was buffered to ≈50 μm, however, removal of external Ca and Mg lead to a four- to fivefold increase in Cs currents and loss of both time-dependent activation and inactivation (reversible upon repletion of external Ca).

These results suggest that (i) permeability ratios forIK1 should account for differences in the degree to which monovalent currents are blocked by extracellular Ca and (ii) extracellular or intracellular divalent cations contribute to the slow phase of activation which may represent either (a) the actual rate of Mg or Ca extrusion from the channel into the cell, a process which may be enhanced by repulsive interaction with the incoming permeant monovalent cation or (b) an intrinsic gating process that is strongly modulated by the permeant monovalent ion and divalent cations.

Key Words

heart inward rectification potassium channel selectivity gating Ca Mg 


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  1. Argibay, J.A., Dutey, P., Ildefonse, M., Ojeda, C., Rougier, O., Tourneur, Y. 1983. Block by Cs of K currentsI K1 and of carbachol induced current in frog atrium.Pfluegers Arch. 397:295–299Google Scholar
  2. Armstrong, C.M. 1981. Sodium channels and gating currents.Physiol. Rev. 61:644–683Google Scholar
  3. Armstrong, C.M., Lopez-Barneo, J. 1987. External calcium ions are required for potassium channel gating.Science 236:712–714Google Scholar
  4. Armstrong, C.M., Swenson, R.P., Taylor, R. 1982. Block of squid axon K channels by internally and externally applied barium ions.J. Gen. Physiol. 80:663–682Google Scholar
  5. Armstrong, C.M., Taylor, S.R. 1980. Interaction of barium ions with potassium channels in squid giant axons.Biophys. J. 30:473–488Google Scholar
  6. Biermans, G., Vereecke, J., Carmeliet, E. 1987. The mechanism of the inactivation of the inward-rectifying K current during hyperpolarizing steps in guinea-pig ventricular myocytes.Pfluegers arch. 410:604–613Google Scholar
  7. Cohen, I.S., DiFrancesco, D., Mulrine, N.K., Pennefather, P. 1989. Internal and external K gate the inward rectifier.Biophys. J. 55:197–202Google Scholar
  8. Cota, G., Armstrong, C. 1988. Potassium channel “inactivation” induced by soft-glass pipettes.Biophys. J. 53:107–109Google Scholar
  9. Frankenhaeuser, B., Hodgkin, A.L. 1957. The action of calcium on the electrical properties of squid axons.J. Physiol. 137:218–244Google Scholar
  10. Fukushima, Y. 1982. Blocking kinetics of the anomalous potassium rectifier of tunicate egg studied by single channel recording.J. Physiol. 331:311–331Google Scholar
  11. Gay, L.A., Stanfield, P.R. 1977. Cs causes a voltage dependent block of inward K currents in resting skeletal muscle fibers.Nature 267:169–170Google Scholar
  12. Grissmer, S., Cahalan, M.D. 1989. Divalent ion trapping inside potassium channels of human T lymphoocytes.J. Gen. Physiol. 93:609–630Google Scholar
  13. Hagiwara, S., Miyazaki, S., Krasne, S., Ciani, S. 1977. Anomalous permeabilities of the egg cell membrane of a starfish in K-T1 mixtures.J. Gen. Physiol. 70:269–281Google Scholar
  14. Hagiwara, S., Miyazaki, S., Moody, W., Patlak, J. 1978. Blocking effects of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg.J. Physiol. 279:167–185Google Scholar
  15. Hagiwara, S., Miyazaki, S., Rosenthal, N.P. 1976. Potassium current and the effect of cesium ion on this current.J. Gen. Physiol. 67:621–638Google Scholar
  16. Hagiwara, S., Takahashi, K. 1974. The anomalous rectification and cation selectivity of the membrane of a starfish egg cell.J. Membrane Biol. 18:61–80Google Scholar
  17. Hamill, O.P., Marty, A., Neher, E., Sakmann, B., Sigworth, F.J. 1981. Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches.Pfluegers Arch. 391:85–100Google Scholar
  18. Harvey, R., Ten Eick, R. 1988. Characterization of the inward-rectifying potassium current in cat ventricular myocytes.J. Gen. Physiol. 91:593–615Google Scholar
  19. Hille, B. 1984. Ionic Channels of Excitable Membranes. p. 231. Sinauer, Sunderland, MAGoogle Scholar
  20. Hille, B., Schwarz, W. 1978. Potassium channels as multi-ion single-file pores.J. Gen. Physiol. 72:409–442Google Scholar
  21. Ishihara, K., Mitsuiye, T., Noma, A., Takano, M. 1989. The Mg2+ block and gating underlying inward rectification of the K+ current in guinea pig cardiac myocytes.J. Physiol. 419:297–320Google Scholar
  22. Katz, B. 1949. Les constantes électriques de la membrane du muscle.Arch. Sci. Physiol. 2:285–299Google Scholar
  23. Kurachi, Y. 1985. Voltage-dependent activation of the inward rectifier potassium channel in the ventricular cell membrane of guinea-pig heart.J. Physiol. 366:365–385Google Scholar
  24. Latorre, R., Miller, C. 1983. Conduction and selectivity in potassium channels.J. Membrane Biol. 71:11–30Google Scholar
  25. Martell, A.E., Smith, R.M. 1977. Critical Stability Constants. pp. 478, 651–652. Plenum, New YorkGoogle Scholar
  26. Matsuda, H. 1988. Open-state substructure of inwardly rectifying potassium channels revealed by magnesium block in guinea-pig heart cells.J. Physiol. 397:237–258Google Scholar
  27. Matsuda, H., Saigusa, A., Irisawa, H. 1987. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg.Nature 325:156–159Google Scholar
  28. Mitra, R., Morad, M. 1985. A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates.Am. J. Physiol. 249:H1056-H1060Google Scholar
  29. Mitra, R., Morad, M. 1987. Permeation and block of the inwardly rectifying K channel in isolated guinea pig ventricular myocytes by divalent and monovalent ions.J. Physiol. 382:128PGoogle Scholar
  30. Mitra, R., Morad, M., Tourneur, Y. 1985. Time-dependent activation of the potassium inward rectifierI K1 in isolated guinea-pig cardiac cells.J. Physiol. 358:52PGoogle Scholar
  31. Mitra, R., Vereecke, J., Carmeliet, E. 1990. Ca and Mg block an intrinsically high Na conductance through a cardiac K channel.Biophys. J. 57:111a Google Scholar
  32. Neyton, J., Miller, C. 1988. Potassium blocks barium permeation through a calcium-activated potassium channel.J. Gen. Physiol. 92:549–567Google Scholar
  33. Ohmori, H. 1978. Inactivation kinetics and steady state current noise in the anomalous rectifier of tunicate egg cell membranes.J. Physiol. 281:77–99Google Scholar
  34. Robinson, R.A., Stokes, R.H. 1965. Electrolyte Solutions. p. 465. Butterworths, LondonGoogle Scholar
  35. Sakmann, B., Trube, G. 1984. Voltage-dependent inactivation of inward-rectifying single channel currents in the guinea-pig heart cell membrane.J. Physiol. 347:659–683Google Scholar
  36. Silver, M., DeCoursey, T.E. 1990. Intrinsic gating of the inward rectifier in bovine pulmonary artery endothelial cells in the presence or absence of internal Mg.J. Gen. Physiol. 96:109–133Google Scholar
  37. Standen, N.B., Stanfield, P.R. 1978. A potential and time-dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions.J. Physiol. 280:169–191Google Scholar
  38. Standen, N.B., Stanfield, P.R. 1979. Potassium depletion and sodium block of potassium currents under hyperpolarization in frog sartorius muscle.J. Physiol. 294:497–520Google Scholar
  39. Tourneur, Y., Mitra, R., Morad, M., Rougier, O. 1987. Activation properties of the inward-rectifying potassium channel on mammalian heart cells.J. Membrane Biol. 97:127–135Google Scholar
  40. Vandenberg, C. 1987. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions.Proc. Natl. Acad. Sci. USA 80:2560–2564Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1991

Authors and Affiliations

  • Raman L. Mitra
    • 1
    • 2
  • Martin Morad
    • 1
    • 2
  1. 1.Department of Internal Medicine, Cardiovascular DivisionUniversity of Pennsylvania School of MedicinePhiladelphia
  2. 2.Department of PhysiologyUniversity of Pennsylvania School of MedicinePhiladelphia

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