P-Glycoprotein Expression in Heart, and its Potential Physiological Relevance

Lazarowski, Alberto

doi:10.19080/jocct.2018.10.555799

Cited by 2 publications

(3 citation statements)

References 35 publications

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“…The potential use of 99m Tc-SESTAMIBI cardio-SPECT, both in resting and effort conditions, could represent noninvasive technologies to detect the risk of acute cardiological failure, and thus, be the telltale heart (Edgar Allan Poe) of SUDEP, in patients with RE. 86 Finally, it is essential to highlight recent advances in using cannabinoids for the treatment of RE. 87 Several mechanisms have been proposed by which cannabinoids could exert their beneficial effects for the most severe types of epilepsy.…”

Section: Glycoprotein In the Heart And Its Potential Role In Sudep De...mentioning

confidence: 99%

“…In contrast, seizures, status epilepticus, and uncontrolled epilepsy may induce cardiac dysfunctions, recalling the “chicken and egg” puzzle concept coined by Friedman, 85 with a high risk of death (SUDEP). The potential use of 99m Tc‐SESTAMIBI cardio‐SPECT, both in resting and effort conditions, could represent noninvasive technologies to detect the risk of acute cardiological failure, and thus, be the telltale heart (Edgar Allan Poe) of SUDEP, in patients with RE 86 …”

Section: Expression Of P‐glycoprotein In the Heart And Its Potential ...mentioning

confidence: 99%

“…The potential use of 99m Tc‐SESTAMIBI cardio‐SPECT, both in resting and effort conditions, could represent noninvasive technologies to detect the risk of acute cardiological failure, and thus, be the telltale heart (Edgar Allan Poe) of SUDEP, in patients with RE. 86 …”

Section: Expression Of P‐glycoprotein In the Heart And Its Potential ...mentioning

confidence: 99%

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Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

2021

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The multidrug-resistance (MDR) phenotype is typically observed in patients with refractory epilepsy (RE) whose seizures are not controlled despite receiving several combinations of more than two antiseizure medications (ASMs) directed against different ion channels or neurotransmitter receptors. Since the use of bromide in 1860, more than 20 ASMs have been developed; however, historically ~30% of cases of RE with MDR phenotype remains unchanged. Irrespective of metabolic biotransformation, the biodistribution of ASMs and their metabolites depends on the functional expression of some ATP-binding cassette transporters (ABC-t) in different organs, such as the blood-brain barrier (BBB), bowel, liver, and kidney, among others. ABC-t, such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP-1), and breast cancer-resistance protein (BCRP), are mainly expressed in excretory organs and play a critical role in the pharmacokinetics (PK) of all drugs. The transporter hypothesis can explain pharmacoresistance to a broad spectrum of ASMs, even when administered simultaneously. Since ABC-t expression can be induced by hypoxia, inflammation, or seizures, a high frequency of uncontrolled seizures increases the risk of RE.These stimuli can induce ABC-t expression in excretory organs and in previously non-expressing (electrically responsive) cells, such as neurons or cardiomyocytes. In this regard, an alternative mechanism to the classical pumping function of P-gp indicates that P-gp activity can also produce a significant reduction in resting membrane potential (ΔΨ0 = −60 to −10 mV). P-gp expression in neurons and cardiomyocytes can produce membrane depolarization and participate in epileptogenesis, heart failure, and sudden unexpected death in epilepsy. On this basis, ABC-t play a peripheral role in controlling the PK of ASMs and their access to the brain and act at a central level, favoring neuronal depolarization by mechanisms independent of ion channels or neurotransmitters that current ASMs cannot control.

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Section: Glycoprotein In the Heart And Its Potential Role In Sudep De...mentioning

confidence: 99%

Section: Expression Of P‐glycoprotein In the Heart And Its Potential ...mentioning

confidence: 99%

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Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

2021

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The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP)

Auzmendi

Akyüz

Lazarowski

2021

Epilepsy & Behavior

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P-Glycoprotein Expression in Heart, and its Potential Physiological Relevance

Cited by 2 publications

References 35 publications

Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP)

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