The long-term goal of this project is to investigate the pharmacological rescue of ion channels that fail to traffic normally to the plasma membrane. Failure of protein trafficking underlies ion channelopathies associated with congenital Long QT2 syndrome (LQT2). Drugs that bind to channels with a high affinity can restore the trafficking defects of mutant ion channels. However, the mechanisms that underlie the drug rescue of these channels remain poorly understood. This proposal examines the differences in pharmacological rescue of Long QT2 trafficking defects at the molecular and functional level.
| Anderson, Corey L; Delisle, Brian P; Anson, Blake D et al. (2006) Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation 113:365-73 |
| Delisle, Brian P; Slind, Jessica K; Kilby, Jennifer A et al. (2005) Intragenic suppression of trafficking-defective KCNH2 channels associated with long QT syndrome. Mol Pharmacol 68:233-40 |
| Foell, Jason D; Balijepalli, Ravi C; Delisle, Brian P et al. (2004) Molecular heterogeneity of calcium channel beta-subunits in canine and human heart: evidence for differential subcellular localization. Physiol Genomics 17:183-200 |
| Delisle, Brian P; Anson, Blake D; Rajamani, Sridharan et al. (2004) Biology of cardiac arrhythmias: ion channel protein trafficking. Circ Res 94:1418-28 |
