Skip to main content
Log in

Effects of β-adrenoceptor stimulation on intracellular Ca transients and tension in rat ventricular muscle

  • Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Effects of β-adrenoceptor stimulation on intracellular Ca2+ transients and tension were explored in rat ventricular muscles injected with aequorin. Adrenaline (0.05–5.0 μM) and isoproterenol (0.05–1.0 μM) increased the peak of twitch tension and accelerated relaxation. The former effect depended on Ca2+ concentration in Tyrode's solution ([Ca2+]o) and the stage of the experiment. Low concentrations of these drugs added to normal Tyrode's solution containing 2 mM [Ca2+]o did not potentiate twitch tension in the early stage of the experiments. These drugs increased the peak of the aequorin light signal and slightly accelerated the falling phase of the light especially the tail. Effects of dibutyryl-cyclic AMP (DB-cAMP) (0.1–5.0 mM) and 3-isobutyl-1-methylxanthine (IBMX) (0.01–0.5 mM) were qualitatively similar to those of adrenaline and isoproterenol.

Isoproterenol applied at the peak of Na-deficient contracture decreased tension without significantly changing the light signal; similar results were obtained in the presence of ryanodine (1 μM).

The results were interpreted as follows: The increase of intracellular cAMP induced by β-adrenoceptor stimulation facilitated Ca2+ uptake by sarcoplasmic reticulum (SR) and decreased Ca2+ sensitivity of contractile elements. Faster relaxation induced by cAMP was considered to be due to the decrease of Ca2+ sensitivity of contractile elements and faster Ca2+ uptake by SR. The slightly faster falling phase of light transient might be due to the faster Ca2+ uptake by SR, which predominates over the slower fall of [Ca2+]i induced by the decreased Ca2+ sensitivity of the contractile element.

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

  • Allen DG, Blinks JR (1978) Calcium transients in aequorin-injected frog cardiac muscle. Nature 273:509–513

    Google Scholar 

  • Allen DG, Kurihara S (1980) Calcium transients in mammalian ventricular muscle. Eur Heart J 1 (Suppl. A):5–15

    Google Scholar 

  • Allen DG, Kurihara S (1982) The effects of muscle length on intracellular calcium transients in mammalian cardiac muscle. J Physiol 327:79–94

    Google Scholar 

  • Allen DG, Eisner DA, Orchard CH (1983) The effects of low sodium solutions on intracellular calcium concentration and tension in ferret ventricular muscle. J Physiol 345:391–407

    Google Scholar 

  • Allen DG, Eisner DA, Orchard CH (1984) Factors influencing free intracellular calcium concentration in quiescent ferret ventricular muscle. J Physiol 350:615–630

    Google Scholar 

  • Blinks JR (1966) Field stimulation as a means of effecting the graded release of autonomic transmitters in isolated heart muscle. J Pharm Exp Ther 151:221–235

    Google Scholar 

  • Blinks JR, Wier WG, Morgan JP, Hess P (1982a) Regulation of intracellular [Ca2+] by cardiotonic drugs. In: Yoshida H et al. (eds). Advances in pharmacology and therapeutics II, vol 3. Pergamon Press, Oxford, pp 205–216

    Google Scholar 

  • Blinks JR, Wier WG, Hess P, Prendergast FG (1982b) Measurement of Ca2+ concentration in living cells. Prog Biophys Mol Biol 40:1–114

    Google Scholar 

  • Cheung WY, Williamson JR (1965) Kinetics of cyclic adenosine monophosphate changes in rat heart following epinephrine administration. Nature 207:979–981

    Google Scholar 

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

    Google Scholar 

  • Endoh M, Blinks JR (1984) Effects of endogenous neurotransmitters on calcium transients in mammalian atrial muscle In: Fleming WW et al (eds) Neuronal and extraneuronal events in autonomic pharmacology. Raven Press, New York, pp 221–230

    Google Scholar 

  • Fabiato A (1981) Myoplasmic free calcium concentration reached during the twitch of an intact isolated cardiac cell and during calcium-induced release calcium from the sarcoplasmic reticulum of skinned cardiac cell from the adult rat or rabbit ventricle. J Gen Physiol 78:457–497

    Google Scholar 

  • Fabiato A (1983) Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245:C1-C14

    Google Scholar 

  • Fabiato A (1985) Effects of ryanodine in skinned cardiac cells. Fed Proc 44:2970–2976

    Google Scholar 

  • Fabiato A, Fabiato F (1975) Relaxing and inotropic effects of cyclic AMP on skinned cardiac cells. Nature 253:556–558

    Google Scholar 

  • Herzig JW, Köhler G, Pfitzer G, Rüegg JC, Wölffle G (1981) Cyclic AMP inhibits contractility of detergent treated glycerol extracted muscle. Pflügers Arch 391:208–212

    Google Scholar 

  • Housmans PR, Lee NKM, Blinks JR (1983) Active shortening retards the decline of the intracellular calcium transient in mammalian heart muscle. Science 221:159–161

    Google Scholar 

  • Kelly JJ Jr, Hoffman BF (1960) Mechanical activity of rat papillary muscle. Am J Physiol 199:157–162

    Google Scholar 

  • Kramers GL, Wells JN (1980) Xanthines and skeletal muscle: Lack of relationship between phosphodiesterase inhibition and increased twitch tension in rat diaphragms. Mol Pharmacol 17:73–78

    Google Scholar 

  • Kurahashi K, Rawlow A, Trendelenburg U (1980) A mathematical model representing the extraneuronal O-methylating system of the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 311:17–32

    Google Scholar 

  • Kurihara S, Allen DG (1982) Intracellular Ca2+ transients and relaxation in mammalian cardiac muscle. Jpn Circ J 46:39–43

    Google Scholar 

  • Kurihara S, Konishi M (1986) Effects of isoproterenol and CO2 acidosis on intracellular Ca transients and tension in rat ventricular muscle. In: Yamada K et al. (eds) Cardiac function under ischemia and hypoxia. The University of Nagoya Press, Nagoya, pp 287–301

    Google Scholar 

  • Marban E, Wier WG (1984) The influence of β-adrenergic stimulation on the relation between intracellular [Ca2+] and tension in intact mammalian cardiac muscle. Biophys J 45:277a

    Google Scholar 

  • Marban E, Rink TJ, Tsien RW, Tsien RY (1980) Free calcium in heart muscle at rest and during contraction measured with Ca2+-sensitive microelectrodes. Nature 286:845–850

    Google Scholar 

  • McClellan GB, Winegrad S (1978) The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle. J Gen Physiol 72:737–764

    Google Scholar 

  • Morgan JP, Blinks JR (1982) Intracellular Ca2+ transient in the cat papillary muscle. Can J Physiol Pharmacol 60:524–528

    Google Scholar 

  • Murad F, Chi Y-M, Rall TW, Sutherland EW (1962) Adenyl cyclase. III. The effect of catecholamines and choline ester on the formation of adenosine 3′,5′-phosphate by preparations from cardiac muscle and liver. J Biol Chem 237:1233–1238

    Google Scholar 

  • Orchard CH, Lakatta EG (1985) Intracellular calcium transient and developed tension in rat heart muscle. J Gen Physiol 86:637–651

    Google Scholar 

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

    Google Scholar 

  • Ray KP, England PJ (1976) Phosphorylation of the inhibitory subunit of troponin and its effect on the calcium dependence of cardiac myofibril adenosine triphosphatase. FEBS Lett 70:11–16

    Google Scholar 

  • Reuter H, Cachelin AB, De Peyer JE, Kokubun S (1983) Modulation of calcium channels in cultured cardiac cells by isoproterenol and 8-bromo-cAMP. Cold Spring Harbor Symp. Quant Biol 48:193–200

    Google Scholar 

  • Robertson SP, Johnson JD, Holroyde MJ, Kranias EG, Potter JD, Solaro RJ (1982) The effect of troponin I phosphorylation on the Ca2+-binding properties of the Ca2+-regulatory site of bovine cardiac troponin. J Biol Chem 257:260–263

    Google Scholar 

  • Schümann HJ, Endoh M, Brodde OE (1975) The time course of the effects of β- and α-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillarly muscle. Naunyn-Schmiedeberg's Arch Pharmacol 289:291–302

    Google Scholar 

  • Solaro RJ, Moir AJS, Perry SV (1976) Phosphorylation of troponin I and the inotropic effect of adrenaline in the perfused rabbit heart. Nature 262:615–617

    Google Scholar 

  • Skelton CL, Levey GS, Epstein SE (1970) Positive inotropic effects of dibutyryl cyclic adenosine 3′,5′-monophosphate. Circ Res 26:35–43

    Google Scholar 

  • Sutko JL, Kenyon JL (1983) Ryanodine modification of cardiac muscle responses to potassium-free solutions. Evidence for inhibition of sarcoplasmic reticulum release. J Gen Physiol 82:385–404

    Google Scholar 

  • Tada M, Katz AM (1982) Phosphorylation of the sarcoplasmic reticulum and sarcolemma. Annu Rev Physiol 44:401–423

    Google Scholar 

  • Tada M, Kirchberger MA, Repke DI, Katz AM (1974) The stimulation of calcium transport in cardiac sarcoplasmic reticulum by adenosine 3′,5′-monophosphate-dependent protein kinase. J Biol Chem 249:6174–6180

    Google Scholar 

  • Tsien RW (1977) Cyclic AMP and contractile activity in heart. Adv Cyclic Nucleotide Res 8:363–420

    Google Scholar 

  • Wier WG, Kort AA, Stern MD, Lakatta EG, Marban E (1983) Cellular calcium fluctuations in mammalian heart. Proc Natl Acad Sci USA 80:7367–7371

    Google Scholar 

  • Yamamoto K, Ohtsuki I (1982) Effect of phosphorylation of porcine cardiac troponin I by 3′:5′-cyclic AMP-dependent protein kinase on the actomyosin ATPase activity. J Biochem 91:1669–1677

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kurihara, S., Konishi, M. Effects of β-adrenoceptor stimulation on intracellular Ca transients and tension in rat ventricular muscle. Pflugers Arch. 409, 427–437 (1987). https://doi.org/10.1007/BF00583798

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00583798

Key words

Navigation