neurology Neurology (from , "string, nerve" and the suffix wikt:-logia, -logia, "study of") is the branch of specialty (medicine) , medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous syst ...

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

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

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

, which causes voltage-gated Na⁺ channels to open, resulting in

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

s. This depolarization 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 blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s has been well studied. It is likely that calcium channel blockers will block

voltage Voltage, also known as (electrical) potential difference, electric pressure, or electric tension, is the difference in electric potential between two points. In a Electrostatics, static electric field, it corresponds to the Work (electrical), ...

and ligand gated calcium channels, thereby affecting calcium-activated potassium channel in

invertebrate Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordata, chordate s ...

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

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

ian

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s, for example, thalamocortical neurons, CA3

pyramidal neurons Pyramidal cells, or pyramidal neurons, are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal cells are the primary excitation units of the mammalian prefrontal cort ...

, 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 noise power, often expressed in deci ...

, and play a vital role in information processing,

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represent ...

. In contrast, the PDSs could be generated by

electrical Electricity is the set of physical phenomena associated with the presence and motion of matter possessing an electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described by Maxwel ...

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 () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

s are assumed to be predominantly generated by activation of the

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitator ...

, 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 predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

. 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.. 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 channels with heavy metals 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; it has 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 to it ...

, 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 area of the head where head hair grows. It is made up of skin, layers of connective and fibrous tissues, and the membrane of the skull. Anatomically, the scalp is part of the epicranium, a collection of structures covering th ...

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.

References

Further reading