Abstract
Looking at an old problem from a new perspective can sometimes lead to new ways of analyzing experimental data which may help in understanding the mechanisms that underlie the phenomena. We show how the application of fractals to analyze the patch clamp recordings of the sequence of open and closed times of cell membrane ion channels has led to a new description of ion channel kinetics. This new information has led to new models that imply: (a) ion channel proteins have many conformational states of nearly equal energy minima and many pathways connecting one conformational state to another, and (b) that these many states are not independent but are linked by physical mechanisms that result in the observed fractal scaling. The first result is consistent with many experiments, simulations, and theories of globular proteins developed over the last decade. The second result has stimulated the suggestion of several different physical mechanisms that could cause the fractal scalings observed.
Similar content being viewed by others
References
Agmon, N.; Hopfield, J.J. CO binding to heme proteins: a model for height distributions and slow conformational changes. J. Chem. Phys. 79:2042–2053; 1983.
Austin, R.H.; Beeson, K.W.; Eisenstein, L.; Frauenfelder, H.; Gunsalus, I.C. Dynamics of ligand binding to myoglobin. Biochem. 14:5355–5373; 1975.
Barnsley, M. Fractals everywhere. New York: Academic Press; 1988.
Barrow, G.M. Physical chemistry, 4th Ed. New York: McGraw Hill; 1961.
Bezanilla, F.; Parsegian, V.A.; Zimmerberg, J. Solute inaccessible aqueous volume changes during opening of the potassium channel of the giant squid axon. Biophys. J. 53:545a; 1988.
Blank, M. The surface compartment model: theory of ion transport focused on ionic processes in the electrical double layers at membrane protein surfaces. Biochim. Biophys. Acta 906:277–294; 1987.
Blatz, A.L.; Magleby, K.L. Quantitative description of three modes of activity of fast chloride channels from rat skeletal muscle. J. Physiol. 378:141–174; 1986.
Careri, G.; Fasella, P.; Gratton, E. Statistical time events in enzymes: a physical assessment. CRC Crit. Rev. Biochem. 3:141–164; 1975.
Carslaw, H.S.; Jaeger, J.C. Conduction of Heat in Solids, 2nd Ed. Oxford: Clarendon Press; 1989.
Catterall, W.A. Structure and function of voltage-sensitive ion channels. Science 242:50–61; 1988.
Condat, C.A.; Jäckle, J. Closed time distribution of ionic channels—analytic solution to a one-dimensional defection diffusion model. Biophys. J. 55:915–925; 1989.
Cox, D.R. Renewal theory. London: Science Paperbacks; 1962.
Croxton, T.L. A model of the gating of ion channels. Biochem. Biophys. Acta 946:19–24; 1988.
Farmer, J.D.; Toffoli, T.; Wolfram, S., Eds. Proceedings of an interdisciplinary workshop on cellular automata. Physica D, 10D:1–247; 1984.
Fishman, H.M. Relaxations, fluctuations and ion transfer across membranes. Prog. Biophys. Molec. Biol. 46:127–162; 1985.
Fitzhugh, R. Impulses and physiological states in theoretical models of nerve membrane. Biophys. J. 1:445–466; 1961.
French, A.S.; Stockbridge, L.L. Fractal and Markov behavior in ion channel kinetics. Can. J. Physiol. Pharm. 66:967–970; 1988.
French, A.S.; Stockbridge, L.L. Potassium channels in human and avian fibroblasts. Proc. R. Soc. Lond. B 232:395–412; 1988.
Glass, L.; Mackey, M.C. From clocks to chaos. Princeton, NJ: Princeton University Press; 1988.
Gleick, J. Chaos: Making a new science. New York: Viking; 1987.
Hille, B. Ionic channels of excitable membranes. Sunderland, MA: Sinauer Associates; 1984.
Hodgkin, A.L.; Huxley, A.F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117:500–544; 1952.
Karplus, M.; McCammon, J.A. The internal dynamics of globular proteins. CRC Crit. Rev. Biochem. 9:293–349; 1981.
Läuger, P. Internal motions in proteins and gating kinetics of ionic channels. Biophys. J. 53:877–884; 1988.
Leuchtag, H.R. Indications of the existence of ferroelectric units in excitable-membrane channels. J. Theor. Biol. 127:321–340; 1987.
Leuchtag, H.R. Phase transitions and ion currents in a model ferroelectric channel unit. J. Theor. Biol. 127:341–359; 1987.
Levitt, D.G. Continuum model of voltage dependent gating. Biophys. J. 55:489–498; 1989.
Liebovitch, L.S.; Fischbarg, J.; Koniarek, J.P.; Todorova, I.; Wang, M. Fractal model of ion-channel kinetics. Biochem. Biophys. Acta. 896:173–180; 1987.
Liebovitch, L.S.; Fischbarg, J.; Koniarek, J.P. Ion channel kinetics: a model based on fractal scaling rather than multistate Markov processes. Math. Biosci. 84:37–68; 1987.
Liebovitch, L.S.; Sullivan, J.M. Fractal analysis of a voltage-dependent potassium channel from cultured mouse hippocampal neurons. Biophys. J. 52:979–988; 1987.
Liebovitch, L.S. The fractal random telegraph signal: signal analysis and applications. Ann. Biomed. Engr. 16:483–494; 1988.
Liebovitch, L.S. Testing fractal and Markov models of ion channel kinetics. Biophys. J. 55:373–377; 1989.
Liebovitch, L.S. Introduction to the properties and analysis of fractal objects, processes, and data. In Marmarelis, V.Z., ed. Advanced Methods of Physiological Systems Modeling Vol. 2. New York: Plenum; 1989:pp. 225–239.
Liebovitch, L.S. Analysis of fractal ion channel gating kinetics: kinetic rates, energy levels, and activation energies. Math. Biosci. 93:97–115; 1989.
Liebovitch, L.S.; Tóth, T.I. A model of ion channel kinetics using deterministic chaotic rather than stochastic processes. Submitted to Biophys. J.
Liebovitch, L.S. Methods of chaos applied to study single channel currents and epithelial ion transport. Invest. Ophthal. Vis. Sci. Suppl. 30:342; 1989.
Machlup, S. Noise in semiconductors: spectrum of a two-parameter random signal. J. Appl. Phys. 25:341–343; 1954.
Machlup, S. Earthquakes, thunderstorms, and other 1/f noises. In Meijer, P.; Mountain, R.; Soulen, R., Jr. eds. Sixth International Conference on Noise in Physical Systems. National Bureau of Standards. Washington, DC: pp. 157–160; 1981.
Mandelbrot, B.B. The fractal geometry of nature. San Francisco: W.H. Freeman and Co.; 1983.
McCammon, J.A.; Harvey, S.C. Dynamics of proteins and nucleic acids. New York: Cambridge University Press; 1987.
Millhauser, G.L.; Salpeter, E.E.; Oswald, R.E. Diffusion models of ion-channel gating and the origin of the power-law distributions from single-channel recording. Proc. Natl. Acad. Sci. USA 85:1503–1507; 1988.
Millhauser, G.L.; Salpeter, E.E.; Oswald, R.E. Rate-amplitude correlation from single-channel records. Biophys. J. 54:1165–1168; 1988.
Millhauser, G.L.; Salpeter, E.E.; Oswald, R.E. Diffusion models of ion channel gating: effects of dimensionality and drift. Biophys. J. 55:554a; 1989.
Neher, E.; Sakmann, B., editors. Single-channel recording. New York: Plenum; 1983.
Pietronero, L.; Tosatti, E., eds. Fractals in physics, New York: North Holland; 1986.
Rae, J.L.; Dewey, J.; Cooper, K. Control of ionic channels in rabbit and corneal endothelium. Biophys. J. 55:496a; 1989.
Rubinson, K.A. Closed channel-open channel equilibrium of the sodium channel of nerve. Biophys. Chem. 25:57–72; 1986.
Rubinson, K.A. The effect of n-pentane on voltage-clamped squid nerve sodium currents. Biophys. Chem. 25:43–55; 1986.
Sauvé, R.; Szabo, G. Interpretation of 1/f fluctuations in ion conducting membranes. J. Theor. Biol. 113:501–516; 1985.
Schuster, H.G. Deterministic chaos, 2nd Ed. New York: VCH; 1988.
Thompson, J.M.T.; Stewart, H.B. Nonlinear dynamics and chaos. New York: John Wiley and Sons; 1988.
Tóth, T.I.; Liebovitch, L.S. A deterministic model of ion channels with chaotic behavior having a Markovian-like probability function. Soc. Neurosci. Abstr. 15:1142; 1989.
Weissman, M.B. 17 f noise and other slow nonexponential kinetics in condensed matter. Reviews of Modern Physics 60:537–571; 1988.
Welch, G.R., Ed. The fluctuating enzyme, New York: John Wiley and Sons; 1986.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Liebovitch, L.S., Tóth, T.I. Using fractals to understand the opening and closing of ion channels. Ann Biomed Eng 18, 177–194 (1990). https://doi.org/10.1007/BF02368428
Issue Date:
DOI: https://doi.org/10.1007/BF02368428