Assessment of neuromodulatory effects of Origanum punonense danin essential oil on AMPA receptor function using whole-cell patch-clamp technique

•Origanum punonense oil was assessed on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.•The whole-cell patch-clamp technique was used to assess the oil effect.•Origanum oil showed an effect on the kinetics of receptor subunit type 2.•Carvacrol-rich oil suggests a potential for neuromodulation. : The quest for natural compounds with neuromodulatory properties has gained significant momentum in neuropharmacology. Among these, Origanum punonense (O. punonense) essential oil (EO) stands out due to its rich bioactive profile, particularly characterized by carvacrol. This study aimed to elucidate the effects of O. punonense EO on α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), crucial synaptic plasticity, and cognitive function mediators. : Leaves of O. punonense were collected along the Dead Sea coast in Jericho. After washing, it was dried in the shade for 15 days and ground. Essential oil was extracted using a microwave-ultrasonic method, with ultrasonic waves to enhance extraction. Using whole-cell patch-clamp techniques, we studied the effects of O. punonense EO on AMPAR kinetics in HEK293t cells transfected with homomeric and heteromeric subunits. : O. punonense EO significantly reduced AMPAR's whole-cell currents, indicating a targeted modulation of synaptic responses. Oil administration inhibited the currents for glutamate receptor subunits GluA1 (reduced from 885±58 pA to 342±20 pA), GluA1/2 (from 627±77 pA to 209±36 pA), GluA2 (from 1125±112 pA to 256±37 pA), and GluA2/3 (from 474±79 pA to 125±31 pA). The EO decreased the desensitization rate significantly for GluA2 and GluA2/3 (p < 0.01) and for GluA1/2 (p < 0.05), except for GluA1. In addition, the EO increased the deactivation rate significantly for GluA2 and GluA2/3 (p < 0.01) and for GluA1/2 (p < 0.05), with no effect observed on GluA1. : This study highlights the possible properties of O. punonense EO and suggests future research to understand its medicinal benefits in neurodegenerative diseases.