Skip to main content
Log in

Use of the cell-attached patch clamp technique to examine regulation of single cardiac K channels by cyclic GMP

  • Invited Paper
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cyclic nucleotides play a central role in the modulation of ion channels in a variety of tissues, including the heart. In order to determine the possible role of cyclic GMP (cGMP) in the regulation of the background K channel activity of cardiac cells, the effect of 8-Br-cGMP on the inwardly-rectifying K channels of cultured ventricular myocytes from embryonic chick hearts was examined. 8-Br-cGMP (10-4 to 10-3 M) inhibited these single channel currents within 3 to 10 min. Spontaneous recovery of the currents occurred with prolonged (≥ 15 min) exposure to 8-Br-cGMP, but this recovery was accompanied by altered channel behavior. Thus, a new long-lasting open state of the channel appeared, in addition to the open state observed prior to 8-Br-cGMP addition. Superfusion of the cells with the muscarinic agonist carbamylcholine (10-5 M) also resulted in inhibition of the currents, which suggests that the cGMP-mediated inhibition of these channels may occur under physiological conditions. Thus, it appears that cGMP may be an important modulator of the background K conductance (and excitability) of cardiac cells.

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.

Similar content being viewed by others

References

  1. Bkaily G, Sperelakis N: Injection of guanosine 5′-cyclic monophosphate into heart cells blocks calcium slow channels. Am J Physiol 248:H745-H749, 1985

    Google Scholar 

  2. Wahler GM, Sperelakis N: Effects of cyclic GMP on single K channel currents in cultured embryonic chick hearts. Fed Proc 45:511, 1986a (Abst)

    Google Scholar 

  3. Wahler GM, Sperelakis N: Cyclic GMP initially causes inhibition of cardiac single K channel currents followed by appearance of long openings. Circulation 74, Suppl II:255, 1986b (Abst)

    Google Scholar 

  4. McLean MJ, Sperelakis N: Retention of fully differentiated electrophysiological properties of chick embryonic heart cells in culture. Devel Biol 50:134–141, 1976

    Google Scholar 

  5. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth F: Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100, 1981

    CAS  PubMed  Google Scholar 

  6. Miller JP, Boswell KH, Muneyama K, Simon LN, Robins RK, Shuman DA: Synthesis and biochemical studies of various 8-substituted derivatives of guanosine- 3′,5′-cyclic phosphate, and xanthosine 3′,5′-cyclic phosphate. Biochem 12:5310–5319, 1973

    Google Scholar 

  7. Lincoln TM, Corbin JD: Characterization and biological role of the cGMP-dependent protein kinase. Adv Cyclic Nucl Res 15:139–192, 1983

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  10. Kurachi Y: Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guinea-pig heart. J Physiol 366:365–385, 1985

    Google Scholar 

  11. 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 401:178–184, 1984

    Google Scholar 

  12. Payet MD, Rousseau E, Sauve R: Single-channel analysis of a potassium inward rectifier in myocytes of newborn rat heart. J Memb Biol 86:79–88, 1985

    Google Scholar 

  13. Soejima MA, Noma A: Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflugers Arch 400:424–431, 1984

    Google Scholar 

  14. Kurachi Y, Nakajimo T, Sugimoto T: Acetylcholine activation of K+ channels in cell-free membrane of atrial cells. Am J Physiol 251:H681-H684, 1986

    Google Scholar 

  15. Pfaffinger PJ, Martin JM, Hunter DD, Nathanson NM, Hille B: GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Nature 317:536–538, 1985

    Google Scholar 

  16. Sorota S, Tsuji Y, Tajima T, Pappano A: Pertussis toxin treatment blocks hyperpolarization by muscarinic agonists in chick atrium. Cric Res 57:748–758, 1985

    Google Scholar 

  17. Yatani A, Codina J, Brown AM, Birnbaumer L: Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk. Science 235:207–211, 1987

    Google Scholar 

  18. Hino N, Ochi R: Effect of acetylcholine on membrane currents in guinea-pig papillary muscle. J Physiol 307:183–197, 1980

    Google Scholar 

  19. Bubien JK, Woods WT: Selective effects of acetylcholine and succinylcholine on potassium channels in heart cells. Physiologist 29:163, 1986 (Abst)

    Google Scholar 

  20. Carmeliet E, Ramon J: Effect of acetylcholine on time-independent currents in sheep cardiac Purkinje fibers. Pflugers Arch 387:207–216, 1980

    Google Scholar 

  21. Carmeliet E, Mubagwa K: Changes by acetylcholine of membrane currents in rabbit cardiac Purkinje fibers. J PHysiol 371:201–217, 1986

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wahler, G.M., Sperelakis, N. Use of the cell-attached patch clamp technique to examine regulation of single cardiac K channels by cyclic GMP. Mol Cell Biochem 80, 27–35 (1989). https://doi.org/10.1007/BF00231001

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00231001

Key words

Navigation