Neurons of the higher brain immediately undergo spreading depolarization (SD) in response to ischemia resulting from heart failure, traumatic brain injury or focal stroke. The current(s) driving SD remain unidentified. At SD onset, neurons cease firing, swell and can die within minutes. To account for the massive SD current, the channel has to be either densely distributed in the plasma membrane, display a high unitary conductance, or both. A study of pyramidal neurons using whole-cell voltage clamp (Czeh et al.