Abstract
1. Quiescent cat papillary muscles were stimulated to contract regularly at Lmax, the length at which force production is optimal, and at 0·85 Lmax. The resulting increase in force production (rate staircase) at each length was characterized as an exponential function.
2. When stimulated from quiescence at 24 min-1 in a bathing fluid [Ca2+] of 2·5 mM, sixteen of twenty-three muscles exhibited biexponential increases in force production at both lengths. The coefficients of the exponential function at Lmax were 1·5-2 times greater than their counterparts at the shorter length, and this length difference was highly significant. When the force staircases were normalized to the peak developed force attained at each length, the number of beats to attain 25, 50, 75, and 98% of peak force at 0·85 Lmax was approximately twice that required at Lmax.
3. At a given length the force staircase (1) exhibited a dependency on the number of beats rather than on stimulation frequency over a range of 12-60 min-1, (2) was accelerated by increasing the bathing fluid [Ca2+] from 1·0 to 5·0 mM, (3) was accelerated in the presence of isoproterenol, and (4) was retarded in the presence of DL-verapamil. Over the entire range of bathing fluid [Ca2+] and at all stimulation frequencies 24 min-1 and above, more beats were required to complete a given level of the normalized staircase at 0·85 Lmax than at Lmax. There was no length difference in the presence of verapamil. These data suggest that transsarcolemmal Ca2+ influx is an important determinant of the kinetics of the force staircase, and the length dependence of the latter indicates that muscle length is an important determinant of transsarcolemmal Ca2+ influx.
4. This conclusion was strengthened by the results of additional studies in which the [Ca2+] of the bathing fluid was abruptly increased from 1·0 to 5·0 mM with the muscle beating in the steady state. The resulting increase in force production (Ca2+ staircase) was described by a monoexponential function with a greater coefficient at Lmax than 0·85 Lmax; when normalized to the peak force difference in the two [Ca2+] at each length, a given level of the staircase was achieved in significantly fewer beats at Lmax than at the shorter length.
5. The data provide a mechanism which, in part, explains the length dependence of excitation-contraction coupling in cardiac muscle with intact sarcolemmae.
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Selected References
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- ABBOTT B. C., MOMMAERTS W. F. A study of inotropic mechanisms in the papillary muscle preparation. J Gen Physiol. 1959 Jan 20;42(3):533–551. doi: 10.1085/jgp.42.3.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allen D. G., Blinks J. R. Calcium transients in aequorin-injected frog cardiac muscle. Nature. 1978 Jun 15;273(5663):509–513. doi: 10.1038/273509a0. [DOI] [PubMed] [Google Scholar]
- Allen D. G., Jewell B. R., Wood E. H. Studies of the contractility of mammalian myocardium at low rates of stimulation. J Physiol. 1976 Jan;254(1):1–17. doi: 10.1113/jphysiol.1976.sp011217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allen D. G. On the relationship between action potential duration and tension in cat papillary muscle. Cardiovasc Res. 1977 May;11(3):210–218. doi: 10.1093/cvr/11.3.210. [DOI] [PubMed] [Google Scholar]
- Bailey L. E., Dresel P. E. Correlation of contractile force with a calcium pool in the isolated cat heart. J Gen Physiol. 1968 Dec;52(6):969–982. doi: 10.1085/jgp.52.6.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beresewicz A., Reuter H. The effects of adrenaline and theophylline on action potential and contraction of mammalian ventricular muscle under "rested-state" and "steady-state" stimulation. Naunyn Schmiedebergs Arch Pharmacol. 1977 Dec;301(2):99–107. doi: 10.1007/BF00501423. [DOI] [PubMed] [Google Scholar]
- Chapman R. A., Niedergerke R. Interaction between heart rate and calcium concentration in the control of contractile strength of the frog heart. J Physiol. 1970 Dec;211(2):423–443. doi: 10.1113/jphysiol.1970.sp009285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chapman R. A., Tunstall J. The dependence of the contractile force generated by frog auricular trabeculae upon the external calcium concentration. J Physiol. 1971 May;215(1):139–162. doi: 10.1113/jphysiol.1971.sp009462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dulhunty A. F., Franzini-Armstrong C. The relative contributions of the folds and caveolae to the surface membrane of frog skeletal muscle fibres at different sarcomere lengths. J Physiol. 1975 Sep;250(3):513–539. doi: 10.1113/jphysiol.1975.sp011068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fabiato A., Fabiato F. Dependence of the contractile activation of skinned cardiac cells on the sarcomere length. Nature. 1975 Jul 3;256(5512):54–56. doi: 10.1038/256054a0. [DOI] [PubMed] [Google Scholar]
- Fabiato A., Fabiato F. Myofilament-generated tension oscillations during partial calcium activation and activation dependence of the sarcomere length-tension relation of skinned cardiac cells. J Gen Physiol. 1978 Nov;72(5):667–699. doi: 10.1085/jgp.72.5.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GROSSMAN A., FURCHGOTT R. F. THE EFFECTS OF FREQUENCY OF STIMULATION AND CALCIUM CONCENTRATION ON CA45 EXCHANGE AND CONTRACTILITY ON THE ISOLATED GUINEA-PIG AURICLE. J Pharmacol Exp Ther. 1964 Jan;143:120–130. [PubMed] [Google Scholar]
- Hibberd M. G., Jewell B. R. Length-dependence of the sensitivity of the contractile system to calcium in rat ventricular muscle [proceedings]. J Physiol. 1979 May;290(2):30P–31P. [PubMed] [Google Scholar]
- Jewell B. R. A reexamination of the influence of muscle length on myocardial performance. Circ Res. 1977 Mar;40(3):221–230. doi: 10.1161/01.res.40.3.221. [DOI] [PubMed] [Google Scholar]
- LANGER G. A. CALCIUM EXCHANGE IN DOG VENTRICULAR MUSCLE: RELATION TO FREQUENCY OF CONTRACTION AND MAINTENANCE OF CONTRACTILITY. Circ Res. 1965 Jul;17:78–89. doi: 10.1161/01.res.17.1.78. [DOI] [PubMed] [Google Scholar]
- Lakatta E. G., Henderson A. H. Starling's Law reactivated. J Mol Cell Cardiol. 1977 May;9(5):347–351. doi: 10.1016/s0022-2828(77)80001-1. [DOI] [PubMed] [Google Scholar]
- Lakatta E. G., Jewell B. R. Length-dependent activation: its effect on the length-tension relation in cat ventricular muscle. Circ Res. 1977 Mar;40(3):251–257. doi: 10.1161/01.res.40.3.251. [DOI] [PubMed] [Google Scholar]
- Langer G. A., Frank J. S., Brady A. J. The myocardium. Int Rev Physiol. 1976;9:191–237. [PubMed] [Google Scholar]
- Langer G. A., Serena S. D., Nudd L. M. Cation exchange in heart cell culture: correlation with effects on contractile force. J Mol Cell Cardiol. 1974 Apr;6(2):149–161. doi: 10.1016/0022-2828(74)90018-2. [DOI] [PubMed] [Google Scholar]
- NIEDERGERKE R. The staircase phenomenon and the action of calcium on the heart. J Physiol. 1956 Dec 28;134(3):569–583. doi: 10.1113/jphysiol.1956.sp005666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Niedergerke R., Page S., Talbot M. S. Calcium fluxes in frog heart ventricles. Pflugers Arch. 1969;306(4):357–360. doi: 10.1007/BF00589161. [DOI] [PubMed] [Google Scholar]
- Parmley W. W., Chuck L. Length-dependent changes in myocardial contractile state. Am J Physiol. 1973 May;224(5):1195–1199. doi: 10.1152/ajplegacy.1973.224.5.1195. [DOI] [PubMed] [Google Scholar]
- Reuter H. Exchange of calcium ions in the mammalian myocardium. Mechanisms and physiological significance. Circ Res. 1974 May;34(5):599–605. doi: 10.1161/01.res.34.5.599. [DOI] [PubMed] [Google Scholar]
- Saari J. T., Johnson J. A. Build-up of calcium content and contractile force in the rabbit heart. Can J Physiol Pharmacol. 1972 Dec;50(12):1206–1210. doi: 10.1139/y72-175. [DOI] [PubMed] [Google Scholar]
- Saari J. T., Johnson J. A. Decay of calcium content and contractile force in the rabbit heart. Am J Physiol. 1971 Dec;221(6):1572–1575. doi: 10.1152/ajplegacy.1971.221.6.1572. [DOI] [PubMed] [Google Scholar]
- Shine K. I., Serena S. D., Langer G. A. Kinetic localization of contractile calcium in rabbit myocardium. Am J Physiol. 1971 Nov;221(5):1408–1417. doi: 10.1152/ajplegacy.1971.221.5.1408. [DOI] [PubMed] [Google Scholar]
- Spurgeon H. A., Thorne P. R., Yin F. C., Shock N. W., Weisfeldt M. L. Increased dynamic stiffness of trabeculae carneae from senescent rats. Am J Physiol. 1977 Apr;232(4):H373–H380. doi: 10.1152/ajpheart.1977.232.4.H373. [DOI] [PubMed] [Google Scholar]
- Toll M. O. Isometric dynamic response of mammalian heart muscle due to step changes in the calcium concentration of the perfusing medium. Recent Adv Stud Cardiac Struct Metab. 1976 May 26;11:159–167. [PubMed] [Google Scholar]
- WALKER S. M. Potentiation and hysteresis induced by stretch and subsequent release of papillary muscle of the dog. Am J Physiol. 1960 Mar;198:519–522. doi: 10.1152/ajplegacy.1960.198.3.519. [DOI] [PubMed] [Google Scholar]
- WINEGRAD S., SHANES A. M. Calcium flux and contractility in guinea pig atria. J Gen Physiol. 1962 Jan;45:371–394. doi: 10.1085/jgp.45.3.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wood E. H., Heppner R. L., Weidmann S. Inotropic effects of electric currents. I. Positive and negative effects of constant electric currents or current pulses applied during cardiac action potentials. II. Hypotheses: calcium movements, excitation-contraction coupling and inotropic effects. Circ Res. 1969 Mar;24(3):409–445. doi: 10.1161/01.res.24.3.409. [DOI] [PubMed] [Google Scholar]