The mechanisms that underlie the different excitability profiles that can be observed from the same neuron in response to current stimulation of varying intensities, and the diversity in excitability profiles exhibited by neurons of the same identified type, can both be mapped to different patterns of ion channel expression. Systematic variation of such patterns can only be done in biophysical models that explicitly take ion channel expression into account. Such models can also explain electrophysiological differences between central and peripheral sinoatrial node cells in mammalian hearts, D1 and D2 medium spiny projection neurons in the striatum, and between young and old pyramidal cells in the rodent hippocampus. The models I will present are based on a new generic formulation for transmembrane current that improves the popular conductance based model in several different ways. I will quickly present the derivation of the generic formulation for transmembrane transport, followed by the construction and analysis of the models mentioned above. If time allows, I will talk about how we are using these next generation of models to study regulation of energy expenditure and food intake through systemic interactions between excitable secretory cells (pancreatic, hypothalamic, pituitary, and muscle cells).