A paroxysmal depolarizing shift (PDS) or depolarizing shift is a hallmark of cellular manifestation of

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

. 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 potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

s. This

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...

is followed by a period of hyperpolarization mediated by Ca²⁺-dependent K⁺ channels or GABA-activated Cl⁻ influx.. 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. In contrast, there lies non-synaptic mechanism of PDS. Unmasking persistent sodium current in presence of calcium channel blockers has been well studied. It is likely that calcium channel blockers will block

voltage Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge t ...

and ligand gated calcium channels, thereby affecting

calcium-activated potassium channel Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that calcium levels inside of a cell ...

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

model systems. The initiation of PDS without blocking any channel is much more prevalent in mammalian

neuron A neuron, neurone, or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...

s, for example, thalamocortical neurons, CA3 pyramidal neurons, and some hypothalamic neurons. The possibility of spontaneous bursting in these neurons is implicated in regulating hormonal secretion. The significance of PDS may increase the

signal-to-noise ratio Signal-to-noise ratio (SNR or S/N) is a measure used in science and engineering that compares the level of a desired signal to the level of background noise. SNR is defined as the ratio of signal power to the noise power, often expressed in d ...

, and play a vital role in

information processing Information processing is the change (processing) of information in any manner detectable by an observer. As such, it is a process that ''describes'' everything that happens (changes) in the universe, from the falling of a rock (a change in posi ...

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circui ...

. In contrast, the PDSs could be generated by

electrical Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described ...

or chemical stimulation of single neurons. 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. The PDS found in invertebrates such as ''Helix'', and higher

vertebrate Vertebrates () comprise all animal taxon, taxa within the subphylum Vertebrata () (chordates with vertebral column, backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the ...

s are assumed to be predominantly generated by activation of the

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the ce ...

, subsequently leading to activation of the

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...

. 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 Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron) ...

.. The amount of calcium entry through ion channels is critical in determining the physiological or pathological state of individual neurons,Pathak et al. (2010), Modulation of Nickel-Induced Bursting with 4-Aminopyridine in Leech Retzius Nerve Cells. http://serbiosoc.org.rs/arch_old/VOL62/SVESKA_4/21%20-%20Pathak.pdf). 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. Alternatively the PDS can still occur and is less frequently studied by blocking

calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables ...

s with

heavy metals upright=1.2, Crystals of lead.html" ;"title="osmium, a heavy metal nearly twice as dense as lead">osmium, a heavy metal nearly twice as dense as lead Heavy metals are generally defined as metals with relatively high density, densities, atomi ...

such as Ni²⁺. Further evidence for Na⁺ dependent PDS is highlighted in leeches with the possibility of studying PDS in detail. It is likely that such type of PDS is sustained in the absence of

Calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

, 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. If several million neurons discharge at once, it shows up on a

scalp The scalp is the anatomical area bordered by the human face at the front, and by the neck at the sides and back. Structure The scalp is usually described as having five layers, which can conveniently be remembered as a mnemonic: * S: The s ...

EEG as a focal

interictal The postictal state is the altered state of consciousness after an epileptic seizure. It usually lasts between 5 and 30 minutes, but sometimes longer in the case of larger or more severe seizures, and is characterized by drowsiness, confusion, nau ...

epileptiform Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

spike. Paroxysmal depolarizing shifts can lead to an

epileptic seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

if there is an underlying predisposition, and recording the spike can be an important aid in distinguishing seizure types.

References

Further reading