In neurology, a paroxysmal depolarizing shift (PDS) or depolarizing shift is a hallmark of cellular manifestation of epilepsy. Little is known about the initiation, propagation and termination of PDS. Previously, electrophysiological studies have provided the evidence that there is a Ca2+-mediated depolarization, which causes voltage-gated Na+ channels to open, resulting in action potentials. This depolarization is followed by a period of hyperpolarization mediated by Ca2+-dependent K+ channels or GABA-activated Cl− influx.[citation needed]. In general, synaptic PDS could be initiated by EPSPs, and the plateau potential of the PDS is maintained by a combination of synaptic potentials (EPSPs, IPSPs) and ionic conductances (persistent sodium current and high-threshold calcium current) and the post-PDS hyperpolarization is governed by multiple potassium currents, activated by calcium or sodium entry, as well as by leak current. The next cycle of depolarization is initiated by both synaptic drive and the hyperpolarization-activated IH current.[citation needed]
Depending on influx of ions, PDS can be theoretically categorized into two types. Ca2+ dependent PDS requires the entry of Ca2+ while Na+ dependent PDS is presumed to be non-synaptic.[1][2]
The PDS found in invertebrates such as Helix, and higher vertebrates are assumed to be predominantly generated by activation of the AMPA receptor, subsequently leading to activation of the NMDA receptor. The evidence shows that there is a probable increase in intracellular calcium ions, which sustain calcium-dependent PDS. As usual, these Ca-ions will activate calcium dependent potassium channels and PDS will terminate. This is the case that provides a clue for synaptic transmission.[citation needed]. The amount of calcium entry through ion channels is critical in determining the physiological or pathological state of individual neurons,[3]). For example, high concentration of calcium perturbs Ca-signalling cascades, leading to the death of neurons and circuits, while adequate amount of calcium will help in maintaining normal physiological function.[citation needed]
Alternatively the PDS can still occur and is less frequently studied by blocking calcium channels with heavy metals such as Ni2+.[1] Further evidence for Na+ dependent PDS is highlighted in leeches with the possibility of studying PDS in detail.[1][4] It is likely that such type of PDS is sustained in the absence of Calcium, the case represents the non-synaptic nature of PDS. Finally, the Na/K pump and calcium activated potassium channel might play a role in terminating PDS. Paradoxically, there might arise the argument whether intracellular calcium could be able to repolarize the single neuron while blocking this calcium entry from the extracellular milieu. However, the other opportunity such as Na+-Ca2+ exchange as well as small contribution from intracellular stores need to be explored.[citation needed]
If several million neurons discharge at once, it shows up on a scalpEEG as a focal interictalepileptiform spike. Paroxysmal depolarizing shifts can lead to an epileptic seizure if there is an underlying predisposition, and recording the spike can be an important aid in distinguishing seizure types.[citation needed]
Ayala, G.F.; Dichter, M.; Gumnit, R.J.; Matsumoto, H.; Spencer, W.A. (1973). "Genesis of epileptic interictal spikes. New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysms". Brain Research. 52: 1–17. doi:10.1016/0006-8993(73)90647-1. PMID4573428.