A methodology for achieving high-speed rates for artificial conductance injection in electrically excitable biological cells

We present a novel approach to implementing the dynamic-clamp protocol (Sharp et al., 1993), commonly used in neurophysiology and cardiac electrophysiology experiments. Our approach is based on real-time extensions to the Linux operating system. Conventional PC-based approaches have typically utiliz...

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Bibliographic Details
Published in:IEEE transactions on biomedical engineering 2001-12, Vol.48 (12), p.1460-1470
Main Authors: Butera, R.J., Wilson, C.G., DelNegro, C.A., Smith, J.C.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biological cells
Cardiology
Cell physiology
Cells
Circuit simulation
Clamps
Computational modeling
Computer operating systems
Computer Simulation
Computerized, statistical medical data processing and models in biomedicine
Control systems
Electric Conductivity
Fundamental and applied biological sciences. Psychology
General aspects. Methods
Ionic conduction
Jitter
Laboratories
Medical control systems
Medical sciences
Membrane Potentials - physiology
Models, Neurological
Molecular and cellular biology
Neurons
Neurons - physiology
Neurophysiology
Neurotransmission
Patch-Clamp Techniques
Protocols
Real time systems
Respiratory System - innervation
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Summary:We present a novel approach to implementing the dynamic-clamp protocol (Sharp et al., 1993), commonly used in neurophysiology and cardiac electrophysiology experiments. Our approach is based on real-time extensions to the Linux operating system. Conventional PC-based approaches have typically utilized single-cycle computational rates of 10 kHz or slower. In this paper, we demonstrate reliable cycle-to-cycle rates as fast as 50 kHz. Our system, which we call model reference current injection (MRCI), pronounced merci, is also capable of episodic logging of internal state variables and interactive manipulation of model parameters. The limiting factor in achieving high speeds was not processor speed or model complexity, but cycle jitter inherent in the CPU/motherboard performance. We demonstrate these high speeds and flexibility with two examples: 1) adding action-potential ionic currents to a mammalian neuron under whole-cell patch-clamp and 2) altering a cell's intrinsic dynamics via MRCI while simultaneously coupling it via artificial synapses to an internal computational model cell. These higher rates greatly extend the applicability of this technique to the study of fast electrophysiological currents such fast Na/sup +/ currents and fast excitatory/inhibitory synapses.
ISSN:0018-9294
1558-2531
DOI:10.1109/10.966605