Skip to main content
Log in

Intracellular protons inhibit inward rectifier K+ channel of guinea-pig ventricular cell membrane

  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

The effect of intracellular protons (Hi +) on the inward rectifier K+ channel of the guinea-pig ventricular cell membrane was examined, using the patch-clamp technique. The inward single-channel current was recorded in “inside-out” and “outside-out” patch configurations, while the pH of the solution perfusing the intra and extracellular side, respectively, was varied. Low intracellular pH (pHi), but not low extracellular pH, inhibited the channel. Low pHi reduced the unit amplitude, which was about 20% smaller at pHi 6.0 than that at pHi 7.4 at every voltage tested. The slope conductance decreased from 41.7 pS at pHi 7.4 to 35.1 pS at pHi 6.0. Low pHi also reduced the channel activity without apparent voltage dependence. The concentration/response curve indicated the half-maximum inhibition at pHi 6.11 and a Hill coefficient of 2.52. Lowering the pHi from 7.4 to 6.0 did not affect the distributions of the open times and the closed times below 50 ms, while the time constant of the histogram constructed from closings longer than 50 ms was approximately doubled. These results indicate that the inward rectifier K+ channel in ventricular myocytes is inhibited by H+ from the intracellular side. This might contribute to the depolarization of the resting membrane potential induced by intracellular acidosis during myocardial ischaemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bielen FV, Bosteels S, Verdonck F (1990) Consequences of CO2 acidosis for transmembrane Na+ transport and membrane current in rabbit cardiac Purkinje fibres. J Physiol (Lond) 427:325–345

    Google Scholar 

  2. Blatz AL (1984) Asymmetric proton block of inward rectifier K channels in skeletal muscle. Pflügers Arch 401:402–407

    Google Scholar 

  3. Bovell DL, Burton FL, Hutter OF, Tian LJ (1990) Effects of decreased internal pH on inwardly rectifying K channels in guinea-pig ventricular cell membrane (abstract). J Physiol (Lond) 429:111P

    Google Scholar 

  4. Boyett MR, Kirby MS, Orchard CH (1988) The effect of acidosis in single ventricular cells isolated from ferret heart (abstract). J Physiol (Lond) 407:114P

    Google Scholar 

  5. Christensen O, Zeuthen T (1987) Maxi K+ channels in leaky epithelia are regulated by intracellular Ca2+, pH and membrane potential. Pflügers Arch 408:249–259

    Google Scholar 

  6. Cook DL, Ikeuchi M, Fujimoto WY (1984) Lowering of pHi inhibits Ca2+-activated K+ channels in pancreatic β-cells. Nature 311:269–271

    Google Scholar 

  7. Cuevas J, Bassett AL, Cameron JS, Furukawa T, Myerburg RJ, Kimura S (1991) Effect of H+ on ATP-regulated K+ channels in feline ventricular myocytes. Am J Physiol 261:H755-H761

    Google Scholar 

  8. Davies NW (1990) Modulation of ATP-sensitive K+ channels in skeletal muscle by intracellular protons. Nature 343:375–377

    Google Scholar 

  9. Hamada E, Takikawa R, Ito H, Iguchi M, Terano A, Sugimoto T, Kurachi Y (1990) Glibenclamide specifically blocks ATP-sensitive K+ channel current in atrial myocytes of guinea pig heart. Jpn J Pharmacol 54:473–477

    Google Scholar 

  10. 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

    Google Scholar 

  11. Harvey RD, Ten Eick RT (1989) On the role of sodium ions in the regulation of the inward-rectifying potassium conductance in cat ventricular myocytes. J Gen Physiol 94:329–348

    Google Scholar 

  12. Irisawa H, Sato R (1986) Intra- and extracellular actions of proton on the calcium current of isolated guinea-pig ventricular cells. Circ Res 59:348–355

    Google Scholar 

  13. Jacobus WE, Taylor GJ, Hollis DP, Nunnally RL (1977) Phosphorus nuclear magnetic resonance of perfused working rat hearts. Nature 265:756–758

    Google Scholar 

  14. Kaibara M, Kameyama M (1988) Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea-pig. J Physiol (Lond) 403:621–640

    Google Scholar 

  15. Kida M, Fujiwara H, Ishida M, Kawai C, Ohura M, Miura I, Yabuuchi Y (1991) Ischemic preconditioning preserves creatinine phosphate and intracellular pH. Circulation 84:2495–2503

    Google Scholar 

  16. Kurachi Y (1982) The effects of intracellular protons on the electrical activity of single ventricular cells. Pflügers Arch 394:264–270

    Google Scholar 

  17. Kurachi Y (1985) Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guineapig heart. J Physiol (Lond) 366:365–385

    Google Scholar 

  18. Matsuda H (1991) Effects of external and internal K+ ions on magnesium block of inwardly rectifying K+ channels in guinea-pig heart cells. J Physiol (Lond) 435:83–99

    Google Scholar 

  19. Mitra R, Morad M (1985) A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates. Am J Physiol 249:H1056-H1060

    Google Scholar 

  20. Moody WJ, Hagiwara S (1982) Block of inward rectification by intracellular H+ in immature oocytes of the starfish Mediaster aequalis. J Gen Physiol 79:115–130

    Google Scholar 

  21. Prod'hom B, Pietrobon D, Hess P (1987) Direct measurement of proton transfer rates to a group controlling the dihydropyridinesensitive Ca2+ channel. Nature 329:243–246

    Google Scholar 

  22. Sakmann B, Trube G (1984) Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol (Lond) 347:641–657

    Google Scholar 

  23. Sakmann B, Trube G (1984) Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol (Lond) 347:659–683

    Google Scholar 

  24. Sato R, Noma A, Kurachi Y, Irisawa H (1985) Effects of intracellular acidification on membrane currents in ventricular cells of guinea-pig. Circ Res 57:553–561

    Google Scholar 

  25. Takano M, Qin D, Noma A (1990) ATP-dependent decay and recovery of K+ channels in guinea pig cardiac myocytes. Am J Physiol 258:H45-H50

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ito, H., Vereecke, J. & Carmeliet, E. Intracellular protons inhibit inward rectifier K+ channel of guinea-pig ventricular cell membrane. Pflügers Arch 422, 280–286 (1992). https://doi.org/10.1007/BF00376214

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00376214

Key words

Navigation