An accompanying poster (Sam et al 2015) on Shakuyaku-kanzo-to (SKT) showed that in normal physiological conditions the threshold for its action in inhibiting contraction in skeletal muscle is relatively high (1 mg/ml) compared to likely therapeutic levels. What could explain how much lower levels can achieve inhibition and why does it not inhibit general skeletal musculature? We determined whether interstitial potassium could be involved since experiments on humans show that interstitial potassium rises substantially during exercise (Green et al, 2000). Using the same methods as in Sam et al (2015), increasing extracellular potassium from 5.4 mM to 10.8 mM itself achieves inhibition of muscle contraction which develops with a time course remarkably similar to that produced by SKT. When SKT is then also applied further inhibition of contraction occurs (Fig 1), but with a much lower threshold concentration, around 0.1 to 0.2 mg/ml. Both interventions might act on a common component of the relevant cell networks to potentiate each other. Further experiments are required to investigate these and other possible explanations. We used the Shorten et al (2007) model to determine whether interstitial [K] changes similar to those recorded experimentally can be predicted. The model was coded in CellML format to enable it to run in OpenCOR (http://www.opencor.ws/). Figure 2 shows that even modest frequencies of stimulation of contraction can achieve a significant rise in interstitial potassium. This model is now being developed to enable hypotheses to be explored that might help to explain the synergy between potassium and SKT