Expressing prior knowledge via model topology and parameter relationships. (A) An example model that captures the kinetic properties of neuronal sodium channels (Kuo and Bean, 1994; Milescu et al., 2010). (B) Various assumptions about the structural and functional elements of the channel are contained in the structure of the model (the states and their connectivity) and in the quantitative relationships between rate constants. The parameter constraints resulting from these assumptions are explained in the text. The α and β quantities are voltage-dependent rate constants, whereas a and b are multiplicative factors expressing allosteric relationships. State labels denote closed (C), closed and inactivated (I), and open (O) states.