The CAD cell line was established from tyrosine hydrolase positive tumours induced in mice carrying the Simian virus 40 large T antigen, and it has been suggested that these ‘immortal’ cells may provide a model of catecholaminergic neurones (Wang and Oxford, 2000). However, electrophysiological studies showed that these cells were depolarized (Vm ~‑40 mV) and unable to generate action potentials unless Vm was deliberately held at a hyperpolarized value (Wang and Oxford, 2000). The aim of the present study was to establish the physiological basis of this depolarized phenotype. As anticipated (Wang and Oxford, 2000), step depolarization to a series of test potentials (VTest) normally evoked transient, inward currents that were followed by a slowly developing but sustained outward current (Fig 1A). Raising [K+]o to 145 mM by iso-osmotically replacing external Na+ abolished the initial transient current (Figure 1B, C) and caused a rightward shift in the steady state current – voltage relationship (Fig 1D). Moreover, under these conditions repolarization at the end of each test pulse evoked a transient inward ‘tail current’ (ITail, Fig 1B) that is carried by K+ entering the cell through channels that had opened during the preceding depolarization. Analysis of the ITail – VTest relationship showed that the half maximal activation of these K+-permeable channels occurred at ~-30 mV (Fig 1E). This observation was surprising since sustained outward current does not normally become apparent until the cells are depolarized past ~‑20 mV (Fig 1D). Indeed, under control conditions, depolarization to -50 – -20 mV evoked small (2 – 3 pA pF-1) but sustained inward currents (Fig D). Since these observations are inconsistent with the hypothesis that the outward current flows via K+ selective channels, subsequent experiments sought to establish the ionic selectivity of the ion channel population underlying the sustained outward current. Cells were therefore depolarized to 70 mV in order to open the voltage-gated conductance fully and Vm then stepped to a series of test potentials. Analysis of the current recorded immediately after the switch to VTest showed that the currents flowing through the open channels reversed at a potential (-37.0±0.01 mV) that differed significantly (P< 0.05) from EK (-85.6 mV). The voltage-gated channels that underlie the sustained outward current thus display relatively poor K+ vs Na+ selectivity. Rather than being dominated by highly selective K+ channels, the membranes of depolarized CAD cells thus display relatively poor ionic selectivity. These cells thus appear to express voltage-gated channels that allow sustained, inward Na+ current and this could well explain why these cells are normally depolarized (Wang and Oxford, 2000). Our data therefore suggest that CAD cells do not retain the biophysical features of mammalian neurones.