Figure 4.

The Dynamic Clamp: A Real Time, Simultaneous Modelling and Experimental Hybrid System. Traditionally, mathematical models have been integrated with experiments via an iterative process: predictions from models are tested against results from appropriate experiments and the models are then updated to address any discrepancies between the two. While this has been, and continues to be, a fruitful endeavour in many cases, hybrid experiments allow the two to be brought together in a real time and interactive fashion. Hybrid systems enable us to manipulate the values of key parameters with the freedom of a mathematical model. At the same time, the effects of these manipulations are observed in real biological systems. One example of a hybrid system is the dynamic clamp protocol for electrically excitable cells [87]. In this system, a mathematical model is used to provide a command signal to the cell from which an electrical recording is being taken. Importantly, since the real-time membrane potential of the cell can be provided to the model, this can be used to inject signals that mimic ionic currents that may or may not be present in the real cell. In this way, parameters associated with these currents can be manipulated, or entirely different channels can be incorporated into the cell. Recently, this method has been used to determine the role of large-conductance potassium (BK) channels in shaping the electrical activity of pituitary cells (see text) [73].