Abstract
This paper presents a mathematical model for analyzing systematic errors associated with the membrane conductance of multicellular muscle preparations as determined in a sucrose gap apparatus. The errors arise because of the interdiffusion of sucrose and saline in the interstitial fluid spaces, which results (a) in spatial variations of equilibrium potentials, membrane conductance, and solution conductivity, and (b) in the existence of a liquid junction potential. The model was applied to simulate the measurement of outward currents predominantly carried by potassium ions; time variations were not considered. Output current/voltage (I/V) curves were computed and compared with the membrane I/V relationship used in the computation. The output curves look very much like experimental results but are distorted considerably from the membrane I/V relationship: (a) under favorable conditions (negligible shunt current), the membrane current is overestimated over the entire range of membrane potential, (b) regions with negative slope conductance of I/V relations with "anomalous rectifier" properties are found to be less pronounced or even absent, and (c) resting potentials may be either increased or reduced. The origin of these errors is related to currents emerging from the sucrose compartment (local circuit as well as externally applied currents). Their dependence on several experimental parameters is discussed.
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- Beeler G. W., Jr, Reuter H. Voltage clamp experiments on ventricular myocarial fibres. J Physiol. 1970 Mar;207(1):165–190. doi: 10.1113/jphysiol.1970.sp009055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berger W., Barr L. Use of rubber membranes to improve sucrose-gap and other electrical recording techniques. J Appl Physiol. 1969 Mar;26(3):378–382. doi: 10.1152/jappl.1969.26.3.378. [DOI] [PubMed] [Google Scholar]
- Brown H. F., Noble D., Noble S. J. The influence of non-uniformity on the analysis of potassium currents in heart muscle. J Physiol. 1976 Jul;258(3):615–629. doi: 10.1113/jphysiol.1976.sp011437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown H. F., Noble S. J. Membrane currents underlying delayed rectification and pace-maker activity in frog atrial muscle. J Physiol. 1969 Oct;204(3):717–736. doi: 10.1113/jphysiol.1969.sp008940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleemann L., Morad M. Potassium currents in frog ventricular muscle: evidence from voltage clamp currents and extracellular K accumulation. J Physiol. 1979 Jan;286:113–143. doi: 10.1113/jphysiol.1979.sp012609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Connor J., Barr L., Jakobsson E. Electrical characteristics of frog atrial trabeculae in the double sucrose gap. Biophys J. 1975 Oct;15(10):1047–1067. doi: 10.1016/S0006-3495(75)85882-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EDWARDS C., KUFFLER S. W., TRAUTWEIN W. Changes in membrane characteristics of heart muscle during inhibition. J Gen Physiol. 1956 Sep 20;40(1):135–145. doi: 10.1085/jgp.40.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giles W., Noble S. J. Changes in membrane currents in bullfrog atrium produced by acetylcholine. J Physiol. 1976 Sep;261(1):103–123. doi: 10.1113/jphysiol.1976.sp011550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldman Y., Morad M. Measurement of transmembrane potential and current in cardiac muscle: a new voltage clamp method. J Physiol. 1977 Jul;268(3):613–654. doi: 10.1113/jphysiol.1977.sp011875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldman Y., Morad M. Regenerative repolarization of the frog ventricular action potential: a time and voltage-dependent phenomenon. J Physiol. 1977 Jul;268(3):575–611. doi: 10.1113/jphysiol.1977.sp011874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODGKIN A. L., HOROWICZ P. The influence of potassium and chloride ions on the membrane potential of single muscle fibres. J Physiol. 1959 Oct;148:127–160. doi: 10.1113/jphysiol.1959.sp006278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HUTTER O. F., NOBLE D. Rectifying properties of heart muscle. Nature. 1960 Nov 5;188:495–495. doi: 10.1038/188495a0. [DOI] [PubMed] [Google Scholar]
- Johnson E. A., Lieberman M. Heart: excitation and contraction. Annu Rev Physiol. 1971;33:479–532. doi: 10.1146/annurev.ph.33.030171.002403. [DOI] [PubMed] [Google Scholar]
- Keenan M. J., Niedergerke R. Intracellular sodium concentration and resting sodium fluxes of the frog heart ventricle. J Physiol. 1967 Jan;188(2):235–260. doi: 10.1113/jphysiol.1967.sp008136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lammel E. A theoretical study on the sucrose gap technique as applied to multicellular muscle preparations. I. Saline-sucrose interdiffusion. Biophys J. 1981 Dec;36(3):533–553. doi: 10.1016/S0006-3495(81)84751-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lammel E., Niedergerke R., Page S. Analysis of a rapid twitch facilitation in the frog heart. Proc R Soc Lond B Biol Sci. 1975 Jun 17;189(1097):577–590. doi: 10.1098/rspb.1975.0073. [DOI] [PubMed] [Google Scholar]
- McGuigan J. A. Some limitations of the double sucrose gap, and its use in a study of the slow outward current in mammalian ventricular muscle. J Physiol. 1974 Aug;240(3):775–806. doi: 10.1113/jphysiol.1974.sp010634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- New W., Trautwein W. Inward membrane currents in mammalian myocardium. Pflugers Arch. 1972;334(1):1–23. doi: 10.1007/BF00585997. [DOI] [PubMed] [Google Scholar]
- Reuter H., Scholz H. A study of the ion selectivity and the kinetic properties of the calcium dependent slow inward current in mammalian cardiac muscle. J Physiol. 1977 Jan;264(1):17–47. doi: 10.1113/jphysiol.1977.sp011656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rougier O., Vassort G., Stämpfli R. Voltage clamp experiments on frog atrial heart muscle fibres with the sucrose gap technique. Pflugers Arch Gesamte Physiol Menschen Tiere. 1968;301(2):91–108. doi: 10.1007/BF00362729. [DOI] [PubMed] [Google Scholar]
- STAEMPFLI R. DIE DOPPELTE SACCHAROSETRENNWANDMETHODE ZUR MESSUNG VON ELEKTRISCHEN MEMBRANEIGENSCHAFTEN MIT EXTRACELLULAEREN ELEKTRODEN. Helv Physiol Pharmacol Acta. 1963;21:189–204. [PubMed] [Google Scholar]
- Trautwein W., McDonald T. F. Current-voltage relations in ventricular muscle preparations from different species. Pflugers Arch. 1978 Apr 25;374(1):79–89. doi: 10.1007/BF00585700. [DOI] [PubMed] [Google Scholar]
- Weidmann S. Electrical constants of trabecular muscle from mammalian heart. J Physiol. 1970 Nov;210(4):1041–1054. doi: 10.1113/jphysiol.1970.sp009256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Hemptinne A. Voltage clamp analysis in isolated cardiac fibres as performed with two different perfusion chambres for double sucrose gap. Pflugers Arch. 1976 May 6;363(1):87–95. doi: 10.1007/BF00587407. [DOI] [PubMed] [Google Scholar]