HCN2 activation modulation: An electrophysiological and molecular study of the well-preserved LCI sequence in the pore channel

• Published in: Archives of biochemistry and biophysics 2020-08, Vol.689, p.108436, Article 108436
• Main Authors: Hernandez, Adan, Hernández-Centeno, Ricardo, Espino-Saldaña, Ángeles E., Martínez-Torres, Ataúlfo
• Format: Article
• Language: English
• Subjects: Gating mechanism; HCN2 pore structure; Ion permeability; Selectivity filter
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2020.108436

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated potassium (Kv) and cyclic nucleotide-gated (CNG) channels. HCN channels contain the glycine-tyrosine-glycine (GYG) sequence that forms part of the selectivity filter, a similar structure than some potassium channels; however, they permeate both sodium and potassium, giving rise to an inward current. Yet a second amino acid sequence, leucine-cysteine-isoleucine (LCI), next to GYG, is well-preserved in all HCNs but not in the selective potassium channels. In this study we used site-directed mutagenesis and electrophysiology in frog oocytes to determine whether the LCI sequence affects the kinetics of HCN2 currents. Permeability and voltage dependence were evaluated, and we found a role of LCI in the gating mechanism combined with changes in ion permeability. The I residue resulted critical to this function. [Display omitted]