Pore-Lining Residues and Intracellular Magnesium Concentration Influence Connexin50 Gap Junction Unitary Channel Conductance

Author

Mary Grace M. Tejada, The University of Western OntarioFollow

Degree

Master of Science

Program

Neuroscience

Supervisor

Dr. Donglin Bai

Abstract

Gap junction (GJ) channels mediate direct intercellular communication. Each GJ channel consists of two hemichannels and each hemichannel is a hexamer of connexins. GJs formed by different connexins display different unitary channel conductance (γ_j) and intracellular magnesium modulation. The underlying mechanisms are not fully clear. The present study investigates the effect of mutating putative pore-lining residues (G8, G46, and V53 individually or together) into glutamate in Cx50 on homotypic GJ channel properties. Expression of the triple and individual mutants in GJ-deficient N2A cells resulted in the formation of functional GJ channels similar to that of Cx50 GJs. However, the γ_js of G8EG46EV53E, G8E, G46E, but not V53E, GJs significantly increased Cx50 GJ γ_j. Increasing intracellular magnesium concentration from 0 to 3 mM significantly reduced the γ_js of Cx50 and all mutant GJs. These results and our homology structural model indicate that these residues are likely pore-lining.

Recommended Citation

Tejada, Mary Grace M., "Pore-Lining Residues and Intracellular Magnesium Concentration Influence Connexin50 Gap Junction Unitary Channel Conductance" (2017). Electronic Thesis and Dissertation Repository. 4616.
https://ir.lib.uwo.ca/etd/4616