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.
Action potential Membrane current Patch clamp Current clamp Voltage clamp Dynamic clamp Dynamic action potential clamp Coupling clamp Cardiac myocytes Computer simulation
This is a preview of subscription content, log in to check access.
Springer Nature is developing a new tool to find and evaluate Protocols. Learn more
We thank Mr. Berend de Jonge and Mr. Jan G. Zegers for expert technical assistance.
Sharp AA, Abbott LF, Marder E (1992) Artificial electrical synapses in oscillatory networks. J Neurophysiol 67:1691–1694PubMedGoogle Scholar
Sharp AA, O’Neil MB, Abbott LF et al (1993) Dynamic clamp: computer-generated conductances in real neurons. J Neurophysiol 69: 992–995PubMedGoogle Scholar
Sharp AA, O’Neil MB, Abbott LF et al (1993) The dynamic clamp: artificial conductances in biological neurons. Trends Neurosci 16: 389–394PubMedCrossRefGoogle Scholar
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
Hutcheon B, Miura RM, Puil E (1996) Models of subthreshold membrane resonance in neocortical neurons. J Neurophysiol 76: 698–714PubMedGoogle Scholar
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
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
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
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
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
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
Barabanov M, Yodaiken V (1997) Introducing real-time Linux. Linux J 34:19–23Google Scholar
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
Clausen C, Valiunas V, Brink PR et al (2013) MATLAB implementation of a dynamic clamp with bandwidth of >125 kHz capable of generating INa at 37 °C. Pflügers Arch 465: 497–507PubMedCentralPubMedCrossRefGoogle Scholar
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
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