The paroxysmal depolarization shift in epilepsy research

•The paroxysmal depolarization shift (PDS) represents the cellular correlate of an interictal spike, which is the electrographic brain surface signal arising from the synchronous occurrence of PDS in many neurons.•Glutamate receptor-mediated currents and currents via L-type voltage gated Ca2+ channels are essential contributors to PDS formation.•In the long term, PDS were suggested to have a pro-epileptic (epileptogenic) role, which may involve excitation-dependent gene transcription and resulting morphological and functional changes.•In the short term, PDS were suggested to have an anti-ictal role, which may involve transient electrical refractoriness of neuronal networks. Several shortcomings with currently available pharmacotherapy of epilepsy necessitate the search for new drug targets. Paroxysmal depolarization shifts (PDS) represent the cellular correlates of electrographic (e.g. interictal) spikes. While the ionic basis of PDS is understood in great detail, controversy exists regarding their proposed implication in epilepsy. To address this issue and to consider potential targetability, this mini-review gives an overview of the ionic conductances contributing to PDS and reflects on the hypotheses of their potential pro-epileptic (epileptogenic) and anti-epileptic roles.