Acetylcholine inhibits activation of the cardiac hyperpolarizing-activated current,i f (original) (raw)

Abstract

Acetylcholine (ACh) in low doses (0.1–1 μM) reversibly inhibits voltage-dependent activation of the “pacemaker” current,i f, in isolated sino-atrial node cells. This action is brought about by a negatively-directed shift of the current activation curve, opposite to that due to catecholamines on the same current. The_i_ f inhibition is anatagonized by atropine, indicating the involvement of muscarinic receptors. In cells incubated in pertussis toxin-containing solutions,i f does not respond to ACh, suggesting that G-proteins mediate the ACh-induced_i_ f depression. Further. ACh can inhibit_i_ f following catecholamine-induced stimulation, but has a negligible effect on_i_ f stimulated by forskolin, a direct activator of adenylate-cyclase. Our results indicate that ACh acts on_i_ f by inhibiting basal adenylatecyclase activity.

Access this article

Log in via an institution

Subscribe and save

Buy Now

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. Breitwieser GE, Szabo G (1985) Uncoupling of cardiac muscarinic and β-adrenergic receptors from ion channels by a guanine nucleotide analogue. Nature 317:538–540
    Google Scholar
  2. Brown HF, DiFrancesco D, Noble SJ (1979) How does adrenaline accelerate the heart? Nature 280:235–236
    Google Scholar
  3. Carmeliet E, Mubagwa K (1986) Characterization of the acetylcholine-induced potassium current in rabbit cardiac Purkinje fibres. J Physiol 371:219–237
    Google Scholar
  4. DiFrancesco D (1985) The cardiac hyperpolarizing-activated current,i f. Origins and developments. Prog Biophys Mol Biol 6:163–183
    Google Scholar
  5. DiFrancesco D (1986) Characterization of single pacemaker channels in cardiac sino-atrial node cells. Nature 324:470–473
    Google Scholar
  6. DiFrancesco D, Ferroni A, Mazzanti M, Tromba C (1986) Properties of the hyperpolarizing-activated current (i f) in cells isolated from the rabbit sino-atrial node. J Physiol 377:61–88
    Google Scholar
  7. Gilman AG (1984) G-proteins and dual control of adenylatecyclase. Cell 36:577–579
    Google Scholar
  8. Hartzell HC, Fischmeister R (1986) Opposite effects of cyclic GMP and cyclic AMP on Ca current in single heart cells. Nature 323:273–275
    Google Scholar
  9. Hescheler J, Kameyama M, Trautwein W (1986) On the mechanism of muscarinic inhibition of the cardiac Ca current. Pflügers Arch 407:182–189
    Google Scholar
  10. Masters SB, Martin MW, Harden TK, Brown JH (1985) Pertussis toxin does not inhibit muscarinic-receptor-mediated phosphoinositide hydrolisis or calcium mobilization. Biochem J 227:933–937
    Google Scholar
  11. Noma A, Trautwein W (1978) Relaxation of the ACh-induced potassium current in the rabbit sino-atrial node. Pflügers Arch 377:193–200
    Google Scholar
  12. Pfaffinger PJ, Martin JM, Hunter DD, Nathanson NM, Hille B (1985) GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Nature 317:536–538
    Google Scholar
  13. Sakmann B, Noma A, Trautwein W (1983) Acetylcholine activation of single muscarinic K channels in isolated pacemaker cells of the mammalian heart. Nature 303:250–253
    Google Scholar
  14. Seamon KB, Padgett W, Daly JW (1981) Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci USA 78:3363–3367
    Google Scholar
  15. Trautwein W (1981) Effects of acetylcholine on the SA node of the heart. In: Carpenter O (ed) Cellular pacemakers: Mechanisms of pacemaker generation. Wiley, New York, pp 127–160
    Google Scholar
  16. Trautwein W (1985) Calcium channels in the membrane of the cardiac myocyte: physiological and pharmacological control. Triangle 24:101–114
    Google Scholar
  17. Tsien RW (1974) Effect of epinephrine on the pacemaker potassium current of cardiac Purkinje fibres. J Gen Physiol 64:293–319
    Google Scholar
  18. Tsien RW, Giles W, Greengard P (1972) Cyclic AMP mediates the effects of adrenaline on cardiac Purkinje fibres. Nature 240:181–183
    Google Scholar

Download references

Author information

Authors and Affiliations

  1. Dipartimento di Fisiologia e Biochimica Generali, Elettrofisiologia, Università di Milano, Via Celoria 26, I-20133, Milano, Italy
    Dario DiFrancesco & Cinzia Tromba

Authors

  1. Dario DiFrancesco
    You can also search for this author inPubMed Google Scholar
  2. Cinzia Tromba
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

DiFrancesco, D., Tromba, C. Acetylcholine inhibits activation of the cardiac hyperpolarizing-activated current,i f.Pflugers Arch. 410, 139–142 (1987). https://doi.org/10.1007/BF00581906

Download citation

Key words