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 (Sha rp et al., 1993), commonly used in neurophysiology and cardiac electrophysi ology experiments. Our approach is based on real-time extensions to the Lin ux operating system. Conventional PC-based approaches have typically utiliz ed 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, wh ich we call model reference current injection (MRCI); pronounced merci is a lso capable of episodic logging of internal state variables and interactive manipulation of model parameters. The limiting factor in achieving high sp eeds was not processor speed or model complexity, but cycle jitter inherent in the CPU/motherboard performance. We demonstrate these high speeds and f lexibility with two examples: 1) adding action-potential ionic currents to a mammalian neuron under whole-cell patch-clamp and 2) altering a cell's in trinsic dynamics via MRCI while simultaneously coupling it via artificial s ynapses to an internal computational model cell. These higher rates greatly extend the applicability of this technique to the study of fast electrophy siological currents such fast Na+ currents and fast excitatory/inhibitory s ynapses.