Skip to main content
SpringerLink
Log in

The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells

  • Excitable Tissues and Central Nervous Physiology
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Ventricular and atrioventricular nodal cells from guinea pig and rabbit hearts were isolated by perfusing the heart with collagenase (Langendorff perfusion). In these cells the cyclic nucleotides cAMP and cGMP or Ca and EGTA were injected through a microelectrode by pressure (0.5–3 kg/cm2). The effect of injection on both the action potential and the hyperpolarization induced by acetylcholine was studied. The following results were obtained.

  1. 1.

    cAMP prolonged the ventricular action potential and shifted the plateau to more positive potentials. The configuration of the A-V nodal action potential was not detectably changed by cAMP injection, but the spontaneous rate was increased.

  2. 2.

    cGMP first shortened the ventricular action potential. In most experiments this effect was followed by long lasting prolongation of the action potential.

  3. 3.

    Both extracellular and intracellular application of dibutyryl cGMP shortened the ventricular action potential but did not produce a subsequent prolongation. However, prolongation was observed on injection of GMP, the direct metabolite.

  4. 4.

    Injection of cGMP in nodal cells did not hyperpolarize the membrane nor slow the spontaneous rate; rather, an increase in rate was observed.

  5. 5.

    The acetylcholine-induced hyperpolarization was not altered in amplitude or time course by the injection of cAMP, cGMP, Ca or EGTA.

  6. 6.

    The results support the hypothesis that cGMP might be involved in the control of voltage-controlled ionic channels but suggest that it does not play a role as a mediator of the classical muscarinic action i.e. the activation of a specific potassium channel by acetylcholine.

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

Access this article

Log in via an institution

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

  • Beresewicz A, Reuter H (1977) The effects of adrenaline and theophilline on action potential and contraction of mammalian ventricular muscle under “rested-state” and “steady-state” stimulation. Naunyn Schmiedeberg's Arch Pharmacol 301: 99–107

    Google Scholar 

  • Brooker G (1977) Dissociation of cyclic GMP from the negative inotropic action of carbachol in guinea pig atria. J Cyclic Nucl Res 3: 407–413

    Google Scholar 

  • Carmeliet E, Ramon J (1980) Effects of acetylcholine on the time-dependent currents in sheep cardiac Purkinje fibers. Pflügers Arch 387: 207–215

    Google Scholar 

  • Diamond J, Ten Eick RT, Trapani AJ (1977) Are increases in cyclic GMP levels responsible for the negative inotropic effects of acetylcholine in the heart? Biochem Biophys Res Comm 79: 912–918

    Google Scholar 

  • Di Francesco D, Noma A, Trautwein W (1980) Separation of current induced by potassium accumulation from acetylcholine-induced relaxation current in the rabbit S-A node. Pflügers Arch 387: 83–90

    Google Scholar 

  • Drummond GI, Severson DL (1979) Cyclic nucleotides and cardiac function. Circ Res 44: 145–153

    Google Scholar 

  • Drummond GI, Hemmings S, Warneboldt RB (1974) Uptake and catabolism of N6,2′-0-dibutyryl cyclic AMP by the perfused heart. Life Sci 15: 319–328

    Google Scholar 

  • Flitney FW, Singh J (1980) Depressant effect of 8-bromo guanosine 3′,5′-cyclic monophosphate on endogeneous adenosine 3′,5′-cyclic monophosphate levels in frog ventricle. J Physiol (Lond) 302: 29P-30P

    Google Scholar 

  • George WJ, Wilkerson RD, Kadowitz PJ (1973) Influence of acetylcholine on contractile force and cyclic nucleotide levels in the isolated perfused rat heart. J Pharmacol Exp Ther 184: 228–235

    Google Scholar 

  • Giles WR, Noble SJ (1976) Changes in membrane currents in bull-frog atrium produced by acetylcholine. J Physiol (Lond) 261: 103–123

    Google Scholar 

  • Glitsch HG, Pott L (1978) Effects of acetylcholine in parasympathic nerve stimulation on membrane potential in quiescent guinea-pig atria. J Physiol (Lond) 279: 655–668

    Google Scholar 

  • Harris EJ, Hutter OH (1956) The action of acetylcholine on the movements of potassium ions in the sinus venosus of the heart. J Physiol (Lond) 133: 58P

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

    Google Scholar 

  • Hoffman BF, Cranefield PF (1960) Electrophysiology of the heart. McGraw Hill, New York

    Google Scholar 

  • Ikemoto Y, Goto M (1975) Nature of the negative inotropic effect of acetylcholine on the myocardium. An elucidation of the bullfrog atrium. Proc Jpn Acad 51: 501–505

    Google Scholar 

  • Isenberg G (1977a) Cardiac Purkinje fibers. Resting, action, and pacemaker potential under the influence of [Ca]i as modified by intracellular injection technique. Pflügers Arch 371: 51–59

    Google Scholar 

  • Isenberg G (1977b) Cardiac Purkinje fibers. The slow inward current component under the influence of modified [Ca]i. Pflügers Arch 371: 61–69

    Google Scholar 

  • Isenberg G (1977c) Cardiac Purkinje fibers [Ca]i controls steady state potassium conductance. Pflügers Arch 371: 71–76

    Google Scholar 

  • Isenberg G (1977d) Cardiac Purkinje fibers. [Ca]i controls the potassium permeability via the conductance componentsg K1 andg K2. Pflügers Arch 371: 77–85

    Google Scholar 

  • Kehoe JS, Marty A (1980) Certain slow synaptic responses: their properties and possible underlying mechanisms. Ann Rev Biophys Bioeng 9: 437–460

    Google Scholar 

  • Kohlhardt M, Haap K (1978) 8-Bromo-guanosine-3′,5′-monophosphate mimics the effect of acetylcholine on slow response action potential and contractile force in mammalian atrial myocardium. J Mol Cell Cardiol 10: 573–586

    Google Scholar 

  • Mirro MJ, Bailey JC, Watanabe AM (1979) Dissociation between the electrophysiological properties and total tissue cyclic guanosine monophosphate content of guinea pig atria. Circ Res 45: 225–233

    Google Scholar 

  • Moustafa E, Skomedal T, Osnes JB, Øye I (1976) Cyclic AMP formation and morphology of myocardial cells isolated from adult heart: Effect of Ca2+ and Mg2+. Biochim Biophys Acta 421: 411–415

    Google Scholar 

  • Nawrath H (1977) Does cyclic GMP mediate the negative inotropic effect of acetylcholine in the heart? Nature 267: 72–74

    Google Scholar 

  • Niedergerke R, Page S (1977) Analysis of catecholamine effects in single atrial trabeculae of the frog heart. Proc R Soc B 197: 33–362

    Google Scholar 

  • Noma A, Trautwein W (1978) Relaxation of the ACh-induced potassium current in the rabbit sinoatrial node cell. Pflügers Arch 377: 193–200

    Google Scholar 

  • Noma A, Peper K, Trautwein W (1979a) Acetylcholine-induced potassium current fluctuations in the rabbit sino-atrial node. Pflügers Arch 381: 263–269

    Google Scholar 

  • Noma A, Osterrieder W, Trautwein W (1979b) The effect of external potassium on the elementary conductance of the ACh-induced potassium channel in the sino-atrial node. Pflügers Arch 381: 263–269

    Google Scholar 

  • Osterrieder W, Noma A, Trautwein W (1980) On the kinetics of the potassium channel activated by acetylcholine in the S-A node of the rabbit heart. Pflügers Arch 386: 101–109

    Google Scholar 

  • Pelzer D, Trautwein W (1981) Zum Mechanismus der negativ inotropen Acetylcholin (ACh)-Wirkung auf das Ventrikelmyokard. German J Cardiol 70: 308: R 202

    Google Scholar 

  • Powell T, Twist VW (1976) Isoprenaline stimulation of cyclic AMP production by isolated cells from adult rat myocardium. Biochem Biophys Res Commun Chem Pathol Pharmacol 72: 1218–1225

    Google Scholar 

  • Powell T, Terrar DA, Twist VW (1978) Electrical activity in superfused cells isolated from adult rat ventricular myocardium. J Physiol (Lond) 284: 148 P

  • Reuter H (1974) Localization of beta adrenergic receptors and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J Physiol (Lond) 242: 429–451

    Google Scholar 

  • Reuter H (1979) Properties of two inward membrane currents in the heart. Ann Rev Physiol 41: 413–424

    Google Scholar 

  • Reuter H, Scholz H (1977) The regulation of the Ca conductance of cardiac muscle by adrenaline. J Physiol (Lond) 264: 49–62

    Google Scholar 

  • Taniguchi J, Kokubun S, Noma A, Irisawa H (1981) Spontaneously active cells isolated from the sino-atrial and atrio-ventricular nodes of the rabbit heart. Jpn J Physiol 31: 547–558

    Google Scholar 

  • Ten Eick R, Nawrath H, McDonald TF, Trautwein W (1976) On the mechanism of negative inotropic effect of acetylcholine. Pflügers Arch 361: 207–213

    Google Scholar 

  • Tsien RW (1973) Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac Purkinje fibres. Nature 245: 120–122

    Google Scholar 

  • Tsien RW, Giles W, Greengard P (1972) Cyclic AMP mediates the effects of adrenaline on cardiac Purkinje fibres. Nature 240: 1821–1823

    Google Scholar 

  • Trautwein W (1963) Generation and conduction fo impulse in the heart as affected by drugs. Pharmacol Rev 15: 277–332

    Google Scholar 

  • Trautwein W, Dudel J (1958) Zum Mechanismus der Membranwirkung des Acetylcholins an der Herzmuskelfaser. Pflügers Arch ges Physiol 266: 324–334

    Google Scholar 

  • Watanabe AM, Besch HR Jr (1975) Interaction between cyclic adenosine monophosphate and cyclic guanosine monophosphate in guinea pig ventricular myocardium. Circ Res 37: 309–317

    Google Scholar 

  • Watanabe AM, McConnaughey MM, Strawbridge RA, Fleming JW, Jones LR, Besch HR Jr (1978) Muscarinic cholinergic receptor modulation of β-adrenergic receptor affinity for catecholamines. J Biol Chem 253: 4833–4836

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Institute for Physiological Sciences, 444, Okazaki, Japan

    W. Trautwein, J. Taniguchi & A. Noma

Authors
  1. W. Trautwein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Noma
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by Japan Soc. for the Promotion of Science. Permanent address: H. Physiologisches Institut der Universität des Saarlandes, D-6650 Homburg (Saar), Federal Republic of Germany

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trautwein, W., Taniguchi, J. & Noma, A. The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells. Pflugers Arch. 392, 307–314 (1982). https://doi.org/10.1007/BF00581624

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00581624

Key words

Search

Navigation