2026-05-05T11:43:06Zhttps://uvadoc.uva.es/oai/request
oai:uvadoc.uva.es:10324/660282024-12-16T11:14:18Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
UVaDOC author Peraza Pérez, Diego Alberto author Cercós, Pilar author Miaja, Pablo author Merinero, Yaiza G. author Lagartera, Laura author Socuéllamos, Paula G. author Izquierdo García, Carolina author Sánchez, Sara A. author López-Hurtado, Alejandro author Martín-Martínez, Mercedes author Olivos-Oré, Luis A. author Naranjo, José R. author Artalejo, Antonio R. author Gutiérrez-Rodríguez, Marta author Valenzuela, Carmen 2024-02-08T16:59:38Z 2024-02-08T16:59:38Z 2019 Front Mol Neurosci . 2019 Feb 4:12:11. doi: 10.3389/fnmol.2019.00011. eCollection 2019. https://uvadoc.uva.es/handle/10324/66028 10.3389/fnmol.2019.00011 Frontiers in Molecular Neuroscience 12 1662-5099 Downstream Regulatory Element Antagonist Modulator (DREAM)/KChIP3/calsenilin is a neuronal calcium sensor (NCS) with multiple functions, including the regulation of A-type outward potassium currents (I A). This effect is mediated by the interaction between DREAM and KV4 potassium channels and it has been shown that small molecules that bind to DREAM modify channel function. A-type outward potassium current (I A) is responsible of the fast repolarization of neuron action potentials and frequency of firing. Using surface plasmon resonance (SPR) assays and electrophysiological recordings of KV4.3/DREAM channels, we have identified IQM-266 as a DREAM ligand. IQM-266 inhibited the KV4.3/DREAM current in a concentration-, voltage-, and time-dependent-manner. By decreasing the peak current and slowing the inactivation kinetics, IQM-266 led to an increase in the transmembrane charge ( Q K V 4.3 / DREAM ) at a certain range of concentrations. The slowing of the recovery process and the increase of the inactivation from the closed-state inactivation degree are consistent with a preferential binding of IQM-266 to a pre-activated closed state of KV4.3/DREAM channels. Finally, in rat dorsal root ganglion neurons, IQM-266 inhibited the peak amplitude and slowed the inactivation of I A. Overall, the results presented here identify IQM-266 as a new chemical tool that might allow a better understanding of DREAM physiological role as well as modulation of neuronal I A in pathological processes. spa Identification of IQM-266, a Novel DREAM Ligand That Modulates KV4 Currents info:eu-repo/semantics/article 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URL https://uvadoc.uva.es/bitstream/10324/66028/1/Identification%20of%20IQM-266%2c%20a%20Novel%20DREAM%20Ligand%20That%20Modulates%20K%20V%204.pdf File MD5 8310c8c2af76627dd909767f007f6c37 4914181 application/pdf Identification of IQM-266, a Novel DREAM Ligand That Modulates K V 4.pdf