Pilocarpine-Induced Status Epilepticus Is Associated with P-Glycoprotein Induction in Cardiomyocytes, Electrocardiographic Changes, and Sudden Death

Pharmaceuticals
Jerónimo AuzmendiAlberto Lazarowski

Abstract

Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistantABCB1-MDR-1gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE. P-gp was also detected after brain or cardiac hypoxia. We have previously demonstrated that repetitive pentylenetetrazole (PTZ)-induced seizures increase P-gp expression in the brain, which is associated with membrane depolarization in the hippocampus, and in the heart, which is associated with fatal SE. SE can produce hypoxic-ischemic altered cardiac rhythm (HIACR) and severe arrhythmias, and both are related with SUDEP. Here, we investigate whether SE induces the expression of hypoxia-inducible transcription factor (HIF)-1α and P-gp in cardiomyocytes, which is associated with altered heart rh...Continue Reading

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Citations

Apr 8, 2020·Frontiers in Behavioral Neuroscience·Jerónimo AuzmendiAlberto Lazarowski
Dec 12, 2020·The European Journal of Neuroscience·Iman Imtiyaz Ahmed Juvale, Ahmad Tarmizi Che Has
Aug 6, 2019·Epilepsy & Behavior : E&B·Daniel Pérez-PérezLuisa Rocha
Mar 2, 2021·Frontiers in Neurology·Enes AkyuzJerónimo Auzmendi
May 9, 2021·Cellular Signalling·Joachim NeumannUlrich Gergs
Jun 11, 2021·Journal of Neuroscience Research·Enes AkyüzMohd Farooq Shaikh
Nov 20, 2021·Clinical and Experimental Pharmacology & Physiology·Inas A HarbEman Hassan Nadwa

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Methods Mentioned

BETA
nuclear translocation

Software Mentioned

SUDEP

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