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AbstractHeart tissue beats synchronously due to the electrical coupling provided by intercellular channels termed gap junction channels. In the ventricles of the heart, these channels are composed of connexin 43 (Cx43); large numbers of these channels localize at the intercalated discs, the site of mechanical as well as electrical coupling in the heart. The colligative properties of these channels support passage of electrical signals from cell to cell, signals that lead all cells of the ventricles (myocytes) to contribute simultaneously to each contraction. Heart attacks, blood clots, or other events that restrict blood flow to (and diffusion of oxygen into) the myocytes for 30 minutes or more, disrupt electrical coupling in the affected (ischemic) region and negatively impact coordinated contraction in the heart, often with deadly effect. Interestingly, loss of blood flow for a brief period of time can protect the heart and electrical coupling from subsequent longer periods of lost blood flow. This protection may, at least in part, reflect phosphorylation, the addition of a phosphate group, to a specific amino acid residue, serine 368 (S368) in the Cx43 protein. Phosphorylation at this residue changes the function of Cx43 channels in a manner that minimizes ischemia-induced damage. In the current project we aim to delineate an accurate time course for phosphorylation of S368, and dephosphorylation of CK1 sites (S325, S328, S330). Dephosphorylation of CK1 sites is associated with ischemic damage. To do so, we are using separate antibodies that specifically detect only the phosphorylated S368 (pS368), and only the phosphorylated CK1 sites (pCK1) in hearts ischemic for 0, 5, 10, 20, and 30’. Results are compared to total Cx43 in the same hearts. Our data suggest that pS368 appears in the first 5-10’ of ischemic time, and that pCK1 levels are reduced simultaneously. Further research into the localization of pS368 and pCK1 Cx43 is necessary to assess the movement of total Cx43 or mechanism of reduction of CK1 Cx43.
Degree ProgramHonors College