سامانه همایش های دانشگاه آزاد اسلامی واحد نجف آباد

صفحه اصلی / اولین همایش بین المللی تحول خدمات سلامت: تلفیق مراقبت، درمان، بازتوانی و امیدبخشی

The Physiological Role of the Mitochondrial Calcium Uniporter (MCU) in Seizure Threshold Regulation: From Mitochondrial Calcium Homeostasis to the GABAergic Inhibitory Network

نویسندگان :

Azadeh Yazdi¹

1- دانشگاه آزاد واحد نجف آباد

کلمات کلیدی :

Mitochondrial Calcium Uniporter (MCU)،Seizure Threshold،GABAergic Neurons،Calcium Homeostasis،Kv7 Potassium Channel

چکیده :

Background: Refractory epilepsy affects approximately 30% of patients, necessitating novel therapeutic targets beyond plasma membrane ion channels. The mitochondrial calcium uniporter (MCU) serves as the primary pathway for Ca²⁺ entry into the mitochondrial matrix, playing a critical role in cytosolic Ca²⁺ buffering, metabolic regulation, and cell fate determination. Methods: This review was conducted through a systematic search of PubMed, Scopus, and Web of Science using keywords related to MCU, epilepsy, seizure threshold, GABAergic neurons, and mitochondrial ion channels. Experimental studies, systematic reviews, and pharmacological articles published up to 2026 were examined. Findings: Evidence demonstrates that MCU deletion produces robust anticonvulsant effects, and notably, deleting MCU specifically in GABAergic (but not glutamatergic) neurons is sufficient for this effect. The proposed mechanism involves enhanced GABAergic synaptic transmission without altering glutamatergic transmission or intrinsic neuronal excitability. MCU inhibition also protects neurons from seizure-induced excitotoxicity. Antiseizure medications such as ethosuximide limit mitochondrial calcium overload through modulation of the MCU complex. Conclusion: MCU is positioned as a selective regulator of seizure threshold through enhancement of GABAergic inhibition. The proposed conceptual model delineates the pathway MCU → mitochondrial Ca²⁺ buffering → cytosolic Ca²⁺ homeostasis → plasma membrane ion channel activity (particularly Kv7/M) → seizure threshold. This framework elevates MCU from a mere pharmacological target to a physiological regulatory node within the inhibitory network, offering novel avenues for developing targeted therapeutic strategies in refractory epilepsy.