Paroxysmal depolarizing shift
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A paroxysmal depolarizing shift (PDS) or depolarizing shift is a cellular manifestation of epilepsy. First, there is a Ca2+ mediated depolarization, which causes voltage gated Na+ to open, resulting in action potentials. This depolarization is followed by a period of hyper-polarization mediated by Ca2+-dependent K+ channels or GABA-activated Cl− influx.
It is noteworthy that unmasking persistent sodium current in presence of Calcium channel blocker has been well established. It is likely that calcium channel blocker will block voltage and ligand gated Calcium channel, thereby affecting calcium-activated potassium channel in invertebrate model system. The initiation of PDS without blocking any channel are much more prevalent in mammalian neurons, for example, thalamocortical neuron, CA3 pyramidal neuron, and some hypothalamic neurons. The possibility of spontaneous bursting in these neurons are implicated in regulating hormonal secretion. The significance of PDS may increase the signal-to-noise ratio, plays vital role in information processing, synaptic plasticity and among others. In contrast, the PDSs could be generated by electrical or chemical stimulation to single neurons.
The PDS found in invertebrates like Helix, and higher vertebrates are assumed to predominantly generated by activation of AMPA receptor subsequently leading to activation of NMDA receptor. The evidence shows that there is probable increase in intracellular calcium ions, which sustained calcium-dependent PDS. As usual, this Ca-ions will activate calcium dependent potassium channel and PDS will terminate. This is the case of that provides clue for synaptic transmission.
Alternatively the PDS can still occur and less frequently studied in blocking calcium channel with heavy metals such as Ni2+. The further evidence for Na+ dependent PDS are highlighted in leech with the possibility to study PDS in detail. It is likely that such type of PDS sustained in 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 able to repolarize the single neuron while blocking these calcium entry from extracellular milleu. However, the other opportunity such as Na+-Ca2+ exchange as well as small contribution from intracellular stores need to be explored.
If several million neurons discharge at once, it shows up on a scalp EEG as a focal interictal epileptiform 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.
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