Neuronal sodium channels: surface density and kinetics
Models of Na+-channels form the basis of our biophysical understanding of action potential (AP) initiation and hence of information encoding. Due to this important role, Na+-channels have been studied for decades1. However, even widely accepted and used Na+-channel models do not pass a fundamental test of consistency (Fig. 1): the current, which a model generates in response to a recorded somatic AP waveform, should be compatible with the notion that the AP upstroke is mainly shaped by the somatic Na+-current: Any large discrepancy between and during the upstroke suggests a faulty model (Fig.1).
This promted us to develop a new model, derived from our own high-resolution measurements, the first measurements to combine minimally invasive cell-attached recordings at single channel resolution with appropriate time resolution necessary to resolve the kinetics of Na+-channel activation (Fig. 2A). We obtained a Markov model for Na+-channel gating that reliably describes the currents evoked by voltage steps (Fig. 2B). Importantly, the model also passes the consistency test (Fig. 2C), although it has not been optimized for this task at all.
The acurate description of somatic Na+-channels (Figure2C) even allows for a quantitative interpretation of the dynamics of action potential waveform. Having directly measured most of the parameters in this equation: , a strict lower bound for the Na+-channel density of 10 channels per can be derived; about twice as much as previously thought. A more elaborate estimate yields even
30 Na+-channels per . We currently use the acurate model and these somatic channel density to obtain a mechanistic understanding of information encodig capabilities of neurons.
Figure 2: A Single channel resolution yields single channel current amplitudes and open probability B Modelled waveforms (gray) closely match measured (black) activation kinetics (bottom) and inactivation properties (top) C The new model passes the consistency test (see Figure 1).
1. Hodgkin and Huxley  pioneered the combination of quantitative analysis of unclamped action potential plus voltage-clamp characterization of selective conductances. Intricate morphology and diverse ion channel populations vastly complicate equivalent studies in mammalian cortical neurons.
 A. L. Hodgkin and A. F. Huxley, J Physiol 117, 4 500 (1952)
 C. M. Colbert and E. Pan, Nat Neurosci 5, 6 533 (2002)
Members working within this Project:Andreas Neef