Gap junction channels (GJCs) permit communication between the cytoplasm of two cells that are in contact. Each GJC is constructed from the union of two connexin hemichannels (Cx-HCs). In last few years, emerging evidence supports a role for Cx-HCs in physiology and pathophysiology as a direct high conductance pathway between the cytoplasm and extracellular medium. Mutations that affect Cx genes could compromise Cx-HC performance and lead to diseased states. My research interest is focused on the study of Cx-HCs, aiming to understand conditions that induce their opening and how these factors correlate with the membrane permeability, maintenance of electrochemical gradients, and incidence of cell death. The goal of my current research is to understand the biophysical changes induced by mutations in Cx26 structure and function that could explain phenotypes observed in syndromic deafness disorders, such as keratitis-ichthyosis-deafness (KID) syndrome. In addition, my colleagues and I are working to identify new mutations in patients with genetic deafness. Our results will facilitate the diagnosis and treatment of deafness in Chilean population.
Using the Xenopus oocyte expression system and primary cultures of the mouse inner ear, I perform electrophysiological (such as whole-cell macroscopic and patch-clamp unitary records) and imaging experiments (such as dye uptake assays and Ca2+-imaging) to study GJC and Cx-HC function and how their dysfunction, because of mutagenesis, contributes to pathophysiology. Taking advantage of these two model systems, I am also interested in understanding how other processes, such as mutations in Cx30 and K+ channels as well as physical trauma and drug-induced ototoxicity, are involved in human deafness.

• Sanchez HA, Slavi N, Srinivas M and Verselis VK. Syndromic deafness mutations at Asn 14 differentially alter the open stability of Cx26 hemichannels. J Gen Physiol 148:25-42, 2016. PMCID: PMC4924935.
• Sanchez HA, Bienkowski R, Slavi N, Srinivas M and Verselis VK. Altered inhibition of Cx26 hemichannels by pH and Zn2+ in the A40V mutation associated with Keratitis-Ichthyosis-Deafness syndrome. J Biol Chem 289: 21519-21532, 2014. PMCID: PMC4118113.
• Sánchez HA, Villone K, Srinivas M and Verselis VK (2013). The D50N mutation and syndromic deafness: Altered Cx26 hemichannel properties caused by effects on the pore and intersubunit interactions. J Gen Physiol 142:3-22, 2013. PMCID:PMC3691445.
• Rubinos C, Sánchez HA, Verselis VK, Srinivas M (2012). Mechanism of inhibition of connexin channels by the quinine derivative N-benzylquininium. J Gen Physiol 139:69-82. PMCID:PMC3250100.
• Sánchez HA, Meşe G, Srinivas M, White TW and Verselis VK (2010). Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause Keratitis-Ichthiosis-Deafness Syndrome. J Gen Physiol 136: 47-62. PMCID:PMC2894548.