Dynamic Clamp as a Tool to Study the Functional Effects of Individual Membrane Currents

  • Géza Berecki
  • Arie O. Verkerk
  • Antoni C. G. van Ginneken
  • Ronald WildersEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1183)


Today, the patch-clamp technique is the main technique in electrophysiology to record action potentials or membrane current from isolated cells, using a patch pipette to gain electrical access to the cell. The common recording modes of the patch-clamp technique are current clamp and voltage clamp. In the current clamp mode, the current injected through the patch pipette is under control while the free-running membrane potential of the cell is recorded. Current clamp allows for measurements of action potentials that may either occur spontaneously or in response to an injected stimulus current. In voltage clamp mode, the membrane potential is held at a set level through a feedback circuit, which allows for the recording of the net membrane current at a given membrane potential.

A less common configuration of the patch-clamp technique is the dynamic clamp. In this configuration, a specific non-predetermined membrane current can be added to or removed from the cell while it is in free-running current clamp mode. This current may be computed in real time, based on the recorded action potential of the cell, and injected into the cell. Instead of being computed, this current may also be recorded from a heterologous expression system such as a HEK-293 cell that is voltage-clamped by the free-running action potential of the cell (“dynamic action potential clamp”). Thus, one may directly test the effects of an additional or mutated membrane current, a synaptic current or a gap junctional current on the action potential of a patch-clamped cell. In the present chapter, we describe the dynamic clamp on the basis of its application in cardiac cellular electrophysiology.

Key words

Action potential Membrane current Patch clamp Current clamp Voltage clamp Dynamic clamp Dynamic action potential clamp Coupling clamp Cardiac myocytes Computer simulation 



We thank Mr. Berend de Jonge and Mr. Jan G. Zegers for expert technical assistance.


  1. 1.
    Sharp AA, Abbott LF, Marder E (1992) Artificial electrical synapses in oscillatory networks. J Neurophysiol 67:1691–1694PubMedGoogle Scholar
  2. 2.
    Sharp AA, O’Neil MB, Abbott LF et al (1993) Dynamic clamp: computer-generated conductances in real neurons. J Neurophysiol 69: 992–995PubMedGoogle Scholar
  3. 3.
    Sharp AA, O’Neil MB, Abbott LF et al (1993) The dynamic clamp: artificial conductances in biological neurons. Trends Neurosci 16: 389–394PubMedCrossRefGoogle Scholar
  4. 4.
    Robinson HPC, Kawai N (1993) Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J Neurosci Meth 49:157–165CrossRefGoogle Scholar
  5. 5.
    Hutcheon B, Miura RM, Puil E (1996) Models of subthreshold membrane resonance in neocortical neurons. J Neurophysiol 76: 698–714PubMedGoogle Scholar
  6. 6.
    Wilders R (2006) Dynamic clamp: a powerful tool in cardiac electrophysiology. J Physiol 576:349–359PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Scott S (1979) Stimulation simulations of young yet cultured beating hearts. PhD thesis, State University of New York at Buffalo, New YorkGoogle Scholar
  8. 8.
    Tan RC, Joyner RW (1990) Electrotonic influences on action potentials from isolated ventricular cells. Circ Res 67:1071–1081PubMedCrossRefGoogle Scholar
  9. 9.
    Joyner RW, Sugiura H, Tan RC (1991) Unidirectional block between isolated rabbit ventricular cells coupled by a variable resistance. Biophys J 60:1038–1045PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Madhvani RV, Xie Y, Pantazis A et al (2011) Shaping a new Ca2+ conductance to suppress early afterdepolarizations in cardiac myocytes. J Physiol 589:6081–6092PubMedCentralPubMedGoogle Scholar
  11. 11.
    Workman AJ, Marshall GE, Rankin AC et al (2012) Transient outward K+ current reduction prolongs action potentials and promotes afterdepolarisations: a dynamic-clamp study in human and rabbit cardiac atrial myocytes. J Physiol 590:4289–4305PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Wilders R, Verheijck EE, Kumar R et al (1996) Model clamp and its application to synchronization of rabbit sinoatrial node cells. Am J Physiol 271:H2168–H2182PubMedGoogle Scholar
  13. 13.
    Butera RJ Jr, Wilson CG, Delnegro CA et al (2001) A methodology for achieving high-speed rates for artificial conductance injection in electrically excitable biological cells. IEEE Trans Biomed Eng 48:1460–1470PubMedCrossRefGoogle Scholar
  14. 14.
    Raikov I, Preyer A, Butera RJ (2004) MRCI: a flexible real-time dynamic clamp system for electrophysiology experiments. J Neurosci Methods 30:109–123CrossRefGoogle Scholar
  15. 15.
    Berecki G, Zegers JG, Verkerk AO et al (2005) HERG channel (dys)function revealed by dynamic action potential clamp technique. Biophys J 88:566–578PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Berecki G, Zegers JG, Bhuiyan ZA et al (2006) Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique. J Physiol 570: 237–250PubMedCentralPubMedGoogle Scholar
  17. 17.
    Verheijck EE, Wilders R, Joyner RW et al (1998) Pacemaker synchronization of electrically coupled rabbit sinoatrial node cells. J Gen Physiol 111:95–112PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Nguyen TP, Xie Y, Garfinkel A et al (2012) Arrhythmogenic consequences of myofibroblast-myocyte coupling. Cardiovasc Res 93:242–251PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Johns DC, Nuss HB, Marbán E (1997) Suppression of neuronal and cardiac transient outward currents by viral gene transfer of dominant-negative Kv4.2 constructs. J Biol Chem 272:31598–31603PubMedCrossRefGoogle Scholar
  20. 20.
    Barabanov M, Yodaiken V (1997) Introducing real-time Linux. Linux J 34:19–23Google Scholar
  21. 21.
    Kemenes I, Marra V, Crossley M et al (2011) Dynamic clamp with StdpC software. Nat Protoc 6:405–417PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Lin RJ, Bettencourt J, White JA et al (2010) Real-Time eXperiment Interface for biological control applications. Conf Proc IEEE Eng Med Biol Soc 2010:4160–4163PubMedCentralPubMedGoogle Scholar
  23. 23.
    Tytgat J (1994) How to isolate cardiac myocytes. Cardiovasc Res 28:280–283PubMedCrossRefGoogle Scholar
  24. 24.
    Barry PH, Lynch JW (1991) Liquid junction potentials and small cell effects in patch clamp analysis. J Membr Biol 121:101–117PubMedCrossRefGoogle Scholar
  25. 25.
    Verkerk AO, Veldkamp MW, de Jonge N et al (2000) Injury current modulates afterdepolarizations in single human ventricular cells. Cardiovasc Res 47:124–132PubMedCrossRefGoogle Scholar
  26. 26.
    Bettencourt JC, Lillis KP, Stupin LR et al (2008) Effects of imperfect dynamic clamp: computational and experimental results. J Neurosci Methods 169:282–289PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Kullmann PHM, Wheeler DW, Beacom J et al (2004) Implementation of a fast 16-bit dynamic clamp using LabVIEW-RT. J Neurophysiol 91:542–554PubMedCrossRefGoogle Scholar
  28. 28.
    Clausen C, Valiunas V, Brink PR et al (2013) MATLAB implementation of a dynamic clamp with bandwidth of >125 kHz capable of generating I Na at 37 °C. Pflügers Arch 465: 497–507PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Wilders R, Verheijck EE, Joyner RW et al (1999) Effects of ischemia on discontinuous action potential conduction in hybrid pairs of ventricular cells. Circulation 99:1623–1629PubMedCrossRefGoogle Scholar
  30. 30.
    Joyner RW, Wang Y-G, Wilders R et al (2000) A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet. Am J Physiol Heart Circ Physiol 279:H752–H763PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Géza Berecki
    • 1
  • Arie O. Verkerk
    • 2
  • Antoni C. G. van Ginneken
    • 2
  • Ronald Wilders
    • 2
    Email author
  1. 1.Health Innovations Research InstituteRMIT UniversityMelbourneAustralia
  2. 2.Department of Anatomy, Embryology and Physiology, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

Personalised recommendations