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Dynamic Clamp in Cardiac and Neuronal Systems Using RTXI

  • Francis A. Ortega
  • Robert J. Butera
  • David J. Christini
  • John A. White
  • Alan D. DorvalIIEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1183)

Abstract

The injection of computer-simulated conductances through the dynamic clamp technique has allowed researchers to probe the intercellular and intracellular dynamics of cardiac and neuronal systems with great precision. By coupling computational models to biological systems, dynamic clamp has become a proven tool in electrophysiology with many applications, such as generating hybrid networks in neurons or simulating channelopathies in cardiomyocytes. While its applications are broad, the approach is straightforward: synthesizing traditional patch clamp, computational modeling, and closed-loop feedback control to simulate a cellular conductance. Here, we present two example applications: artificial blocking of the inward rectifier potassium current in a cardiomyocyte and coupling of a biological neuron to a virtual neuron through a virtual synapse. The design and implementation of the necessary software to administer these dynamic clamp experiments can be difficult. In this chapter, we provide an overview of designing and implementing a dynamic clamp experiment using the Real-Time eXperiment Interface (RTXI), an open-source software system tailored for real-time biological experiments. We present two ways to achieve this using RTXI’s modular format, through the creation of a custom user-made module and through existing modules found in RTXI’s online library.

Key words

Dynamic clamp RTXI Cardiac electrophysiology Neural electrophysiology Neuronal networks Artificial conductance block Reciprocal neuronal coupling 

Notes

Acknowledgments

This work was supported by NIH R01 RR020115 (to D.J.C., R.J.B., and J.A.W.). We thank R.J. Lin for invaluable programming assistance, and F.R. Fernandez for helpful comments regarding this chapter.

References

  1. 1.
    Robinson HP, Kawai N (1993) Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J Neurosci Meth 49:157–165CrossRefGoogle Scholar
  2. 2.
    Sharp AA, O'Neil MB, Marder E (1993) Dynamic clamp: computer-generated conductances in real neurons. J Neurophysiol 69: 992–995PubMedGoogle Scholar
  3. 3.
    Dorval AD, Christini DJ, White JA (2001) Real-Time Linux dynamic clamp: a fast and flexible way to construct virtual ion channels in living cells. Ann Biomed Eng 29:897–907PubMedCrossRefGoogle Scholar
  4. 4.
    Lin RJ, Bettencourt J, White JA et al (2010) Real-time experiment interface for biological control applications. Conf Proc IEEE Eng Med Biol Soc 1:4160–4163Google Scholar
  5. 5.
    Economo MN, Fernandez FR, White JA (2010) Dynamic clamp: alteration of response properties and creation of virtual realities in neurophysiology. J Neurosci 30:2407–2413PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Bettencourt JC, Lillis KP, Stupin LR, White JA (2008) Effects of imperfect dynamic clamp: computational and experimental results. J Neurosci Meth 169:282–289CrossRefGoogle Scholar
  7. 7.
    Livshitz L, Rudy Y (2009) Uniqueness and stability of action potential models during rest, pacing, and conduction using problem-solving environment. Biophysical J 97:1265–1276CrossRefGoogle Scholar
  8. 8.
    Wan X, Laurita KR, Pruvot EJ, Rosenbaum DS (2005) Molecular correlates of repolarization alternans in cardiac myocytes. J Mol Cell Cardiol 12:196–206Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Francis A. Ortega
    • 1
  • Robert J. Butera
    • 2
    • 3
  • David J. Christini
    • 4
  • John A. White
    • 5
  • Alan D. DorvalII
    • 6
    Email author
  1. 1.Greenberg Division of CardiologyWeill Cornell Medical CollegeNew YorkUSA
  2. 2.School of Electrical and Computer EngineeringGeorgia Institute of TechnologyAtlantaUSA
  3. 3.Department of Biomedical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  4. 4.Greenberg Division of Cardiology, Institute for Computational BiomedicineWeill Cornell Medical CollegeNew YorkUSA
  5. 5.Department of Bioengineering, Brain InstituteUniversity of UtahSalt Lake CityUSA
  6. 6.University of UtahSalt Lake CityUSA

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