Abstract
Previously, we reported that concentration jumps of cAMP produced by light flashes in the presence of a photosensitive analogue of cAMP increase the amplitude of the slow inward current (Isi) in isolated bullfrog atrial trabeculae (Nargeot et al. 1983). Here, using newly designed photolabile cyclic nucleotides (Nerbonne et al. 1984a), we have examined the effects of intracellular concentration jumps of cAMP and cGMP on excitation-contraction coupling in frog heart. Concentration jumps of cAMP increase the amplitude and the duration of action potentials, increase Isi and twitch tension. Following single flashes, maximum responses are observed in 10–30 s and recovery times are 30–120 s. The time courses of the cAMP-induced increases in Isi and phasic tension amplitudes are parallel, implying a direct correlation between Ca2+ influx through the slow channels and the development of phasic tension. Although the amplitudes are increased severalfold, cAMP jumps do not measurably alter the kinetics or voltage dependences of the current or tension. cAMP concentration jumps increase the delayed K+ current (IK) and decrease tonic tension; relaxation of contraction is not, however, influenced by cAMP jumps. Concentration jumps of cGMP, on the other hand, have no measurable effects on the action potential, Isi, IK or tension in this preparation.
Similar content being viewed by others
References
Benninger C, Einwachter HM, Haas HG, Kern R (1976) Calcium-sodium antagonism in frog heart: A voltage clamp study. J Physiol (Lond) 259:617–645
Brum G, Flockerzi V, Hofmann F, Osterrieder W, Trautwein W (1983) Injection of the catalytic subunit of cAMP-dependent protein kinase into isolated cardiac myocytes. Pflügers Arch 398:147–154
Carmeliet E, Vereecke J (1969) Adrenaline and the plateau phase of the cardiac action potential: importance of Ca2+, Na+, and K+ conductance. Pflügers Arch 313:300–315
Chapman RA (1979) Excitation-contraction coupling in cardiac muscle. Prog Biophys Molec Biol 35:1–52
Coraboeuf E (1980) Voltage-clamp studies of the slow inward current. In: Zipes DP, Bailey JC, Elharrar V (eds) The slow inward current and cardiac arrhythmias. Martinus Nijhoff, The Hague, The Netherlands
Fabiato A, Fabiato F (1975) Relaxing and inotropic effects of cyclic AMP on skinned cardiac cells. Nature 253:556–558
Fabiato A, Fabiato F (1977) Calcium release from the sarcoplasmic reticulum. Circ Res 40:119–129
Fabiato A, Fabiato F (1978) Calcium-induced release of calcium from the sarcoplasmic reticulum of skinned cells from adult human, dog, cat, rabbit, rat and frog hearts and from foetal hearts and newborn rat ventricles. Ann NY Acad Sci 307:491–522
Fabiato A (1981) Myoplasmic free calcium concentration reached during the twitch of an intact isolated cardiac cell and during calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned cardiac cell from the adult rat or rabbit ventricle. J Gen Physiol 78:457–497
Fozzard HA (1977) Heart: excitation-contraction coupling. Ann Rev Physiol 39:201–220
Garnier D, Rougier O, Gargouil YM, Coraboeuf E (1969) Analyse electrophysiologique du plateau de reponses myocardiques, mise en evidence d'un courant lent entrant en absence d'ions bivalents. Pflügers Arch 313:321–342
Garnier D, Nargeot J, Ojeda C, Rougier O (1978) The action of acetylcholine on the background conductance in frog atrial trabeculae. J Physiol (Lond) 274:381–396
Garnier D, Lester HA, Nargeot J, Nerbonne JM, Richard S (1983) Excitation-contraction coupling in frog atrial muscle during intracellular jumps of cAMP. J Physiol (Lond) 344:38P
Giles W, Noble SJ (1976) Changes in membrane currents in bullfrog atrium produced by acetylcholine. J Physiol (Lond) 261:103–123
Hartzell HC, Titus L (1982) Effects of cholinergic and adrenergic agonists on phosphorylation of a 165,000 dalton myofibrillar protein in intact cardiac muscle. J Biol Chem 257:2111–2120
Horackova M, Vassort G (1979) Sodium-calcium exchange in regulation of cardiac contractility. J Gen Physiol 73:403–424
Lester HA, Nerbonne JM (1982) Physiological and pharmacological manipulations with light flashes. Ann Rev Biophys Bioeng 11:151–175
Mattiazzi AR, Cingolani (1981) Positive inotropic and relaxant effects papaverine on cat papillary muscle. Arch Int Physiol Biochem 89:167–174
Meinertz T, Nawrath H, Scholz H (1975) Relaxant effects of dibutyryl cAMP on mammalian cardiac muscle. J Cyc Nuc Res 1:31–36
Minneman KP, Molinoff P (1980) Classification and quantitation of β-adrenergic receptor subtypes. Biochem Pharmacol 29:1317–1323
Morad M, Trautwein W (1968) The effect of the duration of the action potential on contraction in the mammalian heart muscle. Pflügers Arch 299:66–82
Morad M (1969) Contracture and catecholamines in mammalian myocardium. Science 166:505–506
Morad M, Rolett EL (1972) Relaxing effects of catecholamines on mammalian heart. J Physiol (Lond) 224:537–558
Morad M, Sanders C, Weiss J (1981) The inotropic actions of adrenaline on frog ventricular muscle: relaxing versus potentiating effects. J Physiol (Lond) 311:585–605
Nargeot J, Garnier D, Rougier O (1981) Analysis of the negative inotropic effect of acetycholine on frog atrial fibers. J Physiol (Paris) 77:829–843
Nargeot J, Lester HA, Birdsall NJM, Stockton J, Wassermann NH, Erlanger BF (1982) A photoisomerizable muscarinic antagonist: studies of a binding and conductance relaxations in frog heart. J Gen Physiol 79:657–678
Nargeot J, Nerbonne JM, Engels J, Lester HA (1983) Time course of the increase in the myocardial slow inward current after a photochemically generated concentration jump of intracellular cAMP. Proc Natl Acad Sci USA 80:2395–2399
Nerbonne JM, Richard S, Nargeot J, Lester HA (1984a) New photoactivatable cyclic nucleotides produce intracellular jumps in cyclic AMP and cyclic GMP concentrations. Nature, vol 310, no 5972, pp 74–76
Nerbonne JM, Richard S, Nargeot J (1984b) Ca2+ channels are unblocked within a few ms after photoremoval of nifedipine. J Mol Cell Cardiol in press
Ochi R, Trautwein W (1971) The dependence of cardiac contraction on depolarization and slow inward current. Pflügers Arch 323:187–203
Opie L (1982) Role of cyclic nucleotides in heart metabolism. Cardiovas Res 16:483–507
Osterrieder W, Brum G, Hescheler J, Trautwein W, Hofmann F, Flockerzi V (1982) Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature 298:576–578
Ouedraogo CO, Garnier D, Nargeot J, Pourrias B (1982) Electrophysiological and pharmacological study of the inotropic effects of adrenaline, dopamine and tryptamine on frog atrial fibers. J Mol Cell Cardiol 14:111–121
Reuter H, Scholz H (1977) The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol (Lond) 264:49–62
Reuter H (1979) Properties of two inward membrane currents in the heart. Ann Rev Physiol 41:413–424
Reuter H (1982) Na−Ca countertransport in cardiac muscle. In: Martonosi A (ed) Membranes and transport, vol 1. Plenum Press, New York, pp 623–631
Reuter H (1983) Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301:569–574
Rinaldi ML, LePeuch CJ, Demaille JG (1981) The epinephrine-induced activation of the cardiac slow Ca2+ channel is mediated by the cAMP-dependent phosphorylation of calciductin, a 23,000 Mr sarcolemmal protein. FEBS Lett 129:277–281
Rinaldi ML, Capony J-P, Demaille JG (1982) The cyclic AMP-dependent modulation of cardiac sarcolemmal slow calcium channels. J Mol Cell Cardiol 14:277–289
Robison GA, Butcher RW, Oye I, Morgan HE, Sutherland EW (1965) The effect of epinephrine on adenosine-3′,5′-phosphate levels in the isolated, perfused rat heart. Mol Pharmacol 1:168–177
Roulet M-J, Mongo KG, Vassort G, Ventura-Clapier R (1979) The dependence of twitch tension on sodium ions and on internal Ca2+ stores in voltage-clamped frog atrial fibers. Pflügers Arch 379:259–268
Shine KI, Serena SD, Langer GA (1971) Kinetic localization of contractile calcium in rabbit myocardium. Am J Physiol 221:1408–1417
Ten Eick R, Nawrath H, McDonald TF, Trautwein W (1976) On the mechanism of the negative inotropic effect of acetylcholine. Pflügers Arch 361:207–213
Trautwein W, McDonald TF, Tripathi O (1975) Calcium conductance and tension in mammalian ventricular muscle. Pflügers Arch 354:55–74
Trautwein W, Taniguchi J, Noma A (1982) The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells. Pflügers Arch 392:307–314
Tsien RW (1973) Adrenaline-like effects of intracellular iontophoresis of cAMP in cardiac Purkinje fibers. Nature New Biol 245:120–121
Tsien RW (1977) Cyclic AMP and contractile activity in the heart. Adv Cyc Nuc Res 8:363–420
Tsien RW (1983). Calcium channels in exitable membranes. Ann Rev Physiol 45:341–358
Tsien RW, Weingart R (1976) Inotropic effect of cyclic AMP in calf ventricular muscle studied by the cut end method. J Physiol (Lond) 260:117–141
Vassort G (1973) Influence of sodium ions on the regulation of frog myocardial contractility. Pflügers Arch 339:225–240
Vassort G, Rougier O, Garnier D, Sauviat MP, Coraboeuf E, Gargouil YM (1969) Effects of adrenaline on membrane currents during the cardiac action potential. Pflügers Arch 309:70–81
Vassort G, Horackova M, Mongo K, Roulet M-J, Ventura-Clapier R (1979) Transmembrane calcium movements and excitation-contraction coupling in myocardial cells. Path Biol 27:21–29
Vogel S, Sperelakis N (1981) Induction of slow action potentials by microiontophoresis of cyclic AMP into heart cells. J Mol Cell Cardiol 13:51–64
Yamasaki Y, Fujiwara M, Toda N (1974) Effects of intracellularly applied cyclic 3′,5′-adenosine monophosphate and dibutyryl cyclic 3′,5′-adenosine monophosphate on the electrical activity of sino-atrial cells of the rabbit. J Pharmacol Exp Ther 190:15–20
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Richard, S., Nerbonne, J.M., Nargeot, J. et al. Photochemically produced intracellular concentration jumps of cAMP mimic the effects of catecholamines on excitation-contraction coupling in frog atrial fibers. Pflugers Arch. 403, 312–317 (1985). https://doi.org/10.1007/BF00583606
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00583606