Phosphorylation at Connexin43 Serine-368 Is Necessary for Myocardial Conduction During Metabolic Stress
Division of Cardiovascular Medicine, Department of Medicine
Biochemical Phenomena, Metabolism, and Nutrition | Cardiology | Cardiovascular Diseases | Cellular and Molecular Physiology | Genetic Phenomena
Connexin43 (Cx43) phosphorylation alters gap junction localization and function. In particular, phosphorylation at serine-368 (S368) has been suggested to alter gap junctional conductance, but previous reports have shown inconsistent results for both timing and functional effects of S368 phosphorylation. The objective of this study was to determine the functional effects of isolated S368 phosphorylation. We evaluated wild-type Cx43 (AdCx43) and mutations simulating permanent phosphorylation (Ad368E) or preventing phosphorylation (Ad368A) at S368. Function was assessed by optical mapping of electrical conduction in patterned cultures of neonatal rat ventricular myocytes, under baseline and metabolic stress (MS) conditions. Baseline conduction velocity (CV) was similar for all groups. In the AdCx43 and Ad368E groups, MS moderately decreased CV. Ad368A caused complete conduction block during MS. Triton-X solubility assessment showed no change in Cx43 location during conduction impairment. Western blot analysis showed that Cx43-S368 phosphorylation was present at baseline, and that it decreased during MS. Our data indicate that phosphorylation at S368 does not affect CV under baseline conditions, and that preventing S368 phosphorylation makes Cx43 hypersensitive to MS. These results show the critical role of S368 phosphorylation during stress conditions.
conduction velocity, connexin43, metabolic stress, phosphorylation, serine 368
DOI of Published Version
J Cardiovasc Electrophysiol. 2016 Jan;27(1):110-9. doi: 10.1111/jce.12833. Epub 2015 Oct 13. Link to article on publisher's site
Journal of cardiovascular electrophysiology
Nassal, Michelle M. J.; Werdich, Andreas A.; Wan, Xiaoping; Hoshi, Malcolm; Deschenes, Isabelle; Rosenbaum, David S.; and Donahue, J. Kevin, "Phosphorylation at Connexin43 Serine-368 Is Necessary for Myocardial Conduction During Metabolic Stress" (2016). Cardiovascular Medicine Publications and Presentations. 99.