Paroxysmal depolarizing shift
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 evidences 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 hyper-polarization 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. It is noteworthy that unmasking persistent sodium current in presence of Calcium channel blocker has been well studied. 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.
Depending on influx of ions, PDS can be theoretically categorized into two type. 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 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.. The amount of calcium entry through ion channel is critical to determine the physiological or pathological state of individual neuron [3], [4]). For example, high concentration of the calcium leads to perturb Ca-signalling cascades leading to death of neurons and circuit, while adequate amount of calcium will help in maintaining normal physiological function [5].
Alternatively the PDS can still occur and less frequently studied in blocking calcium channel with heavy metals such as Ni2+.[1] The further evidence for Na+ dependent PDS are highlighted in leech with the possibility to study PDS in detail.[1][6] 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.
References
- 1 2 3 Pathak, Dhruba; Lopicic, Srdjan; Stanojevic, Marija; Nedeljkov, Aleksandra; Pavlovic, Dragan; Cemerikic, Dusan; Nedeljkov, Vladimir (2009). "Ethanol and magnesium suppress nickel-induced bursting activity in leech Retzius nerve cells" (PDF). General Physiology and Biophysics. 28 Spec No: 9–17. PMID 19893074.
- ↑ Üre, Atik; Altrup, Ulrich (2006). "Block of spontaneous termination of paroxysmal depolarizations by forskolin (buccal ganglia, Helix pomatia)". Neuroscience Letters. 392 (1–2): 10–5. doi:10.1016/j.neulet.2005.08.045. PMID 16171948.
- ↑ Pathak D (2017), Paroxysmal Depolarization Shift in Leech Retzius Nerve Cells Revisited. MOJ Anat & Physiol 3(1): 00077. DOI: 10.15406/mojap.2017.03.00077. http://medcraveonline.com/MOJAP/MOJAP-03-00077.pdf
- ↑ 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
- ↑ Pathak D (2017), Paroxysmal Depolarization Shift in Leech Retzius Nerve Cells Revisited. MOJ Anat & Physiol 3(1): 00077. DOI: 10.15406/mojap.2017.03.00077. http://medcraveonline.com/MOJAP/MOJAP-03-00077.pdf
- ↑ Angstadt, JD; Choo, JJ (1996). "Sodium-dependent plateau potentials in cultured Retzius cells of the medicinal leech". Journal of Neurophysiology. 76 (3): 1491–502. PMID 8890269.
Further reading
- Epilepsy and Seizures at eMedicine
- Epileptiform Discharges at eMedicine
- https://web.archive.org/web/20090220231627/http://www.aesnet.org/index.cfm?objectid=AB567D39-E7FF-0F41-282DBE7D52DE97DF%5Bfull+citation+needed%5D
- 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. PMID 4573428.
- Bromfield, Edward B; Cavazos, José E; Sirven, Joseph I, eds. (2006). "Basic Mechanisms Underlying Seizures and Epilepsy". An Introduction to Epilepsy. West Hartford: American Epilepsy Society.