Effects of imperfect dynamic clamp: computational and experimental results.
In the dynamic clamp technique, a typically nonlinear feedback system delivers electrical current to an excitable cell that represents the actions of "virtual" ion channels (e.g., channels that are gated by local membrane potential or by electrical activity in neighboring biological or virtual neurons). Since the conception of this technique, there have been a number of different implementations of dynamic clamp systems, each with differing levels of flexibility and performance. Embedded hardware-based systems typically offer feedback that is very fast and precisely timed, but these systems are often expensive and sometimes inflexible. PC-based systems, on the other hand, allow the user to write software that defines an arbitrarily complex feedback system, but real-time performance in PC-based systems can be deteriorated by imperfect real-time performance. Here, we systematically evaluate the performance requirements for artificial dynamic clamp knock-in of transient sodium and delayed rectifier potassium conductances. Specifically, we examine the effects of controller time step duration, differential equation integration method, jitter (variability in time step), and latency (the time lag from reading inputs to updating outputs). Each of these control system flaws is artificially introduced in both simulated and real dynamic clamp experiments. We demonstrate that each of these errors affect dynamic clamp accuracy in a way that depends on the time constants and stiffness of the differential equations being solved. In simulations, time steps above 0.2ms lead to catastrophic alteration of spike shape, but the frequency-current relationship is much more robust. Latency (the part of the time step that occurs between measuring membrane potential and injecting re-calculated membrane current) is a crucial factor as well. Experimental data are substantially more sensitive to inaccuracies than simulated data.
Bettencourt
Jonathan C
JC
Boston University, Department of Biomedical Engineering, Boston, MA 02215, USA.
Lillis
Kyle P
KP
Stupin
Laura R
LR
White
John A
JA
D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000295:instrumentation*; D051381:Rats; D020318:Rats, Long-Evans
D007473:Ion Channels