The goal of this research is to understand the extrinsic influences and intrinsic structures responsible for the function and modulation of the cardiac G protein-gated potassium channel.
The first aim i s to determine whether a phosphatase impacts the function of GIRK channels in a subunit-dependent fashion. The GIRK1/GIRK4 heteromultimer (IKAch) and the GIRK4 homomultimer studied in atrial myocytes from wild-type and GIRK1 knockout mice, respectively, exhibit distinct functional properties, including different susceptibilities to rundown in the cell-attached patch configuration. The hypothesis that a phosphatase exhibiting a relative selectivity for GIRK4 homomultimeric channels is responsible for this difference will be tested. The experiments proposed in this aim could reveal a mechanism whereby cells segregate the functional consequences of parallel branches of a complex signaling cascade.
The second aim i s to develop an expression system involving atrial myocytes lacking GIRK1 or GIRK4 to evaluate channel structure-function relationships in a native setting. Such a system will offer a unique opportunity to perform structure/function analyses of a cardiac ion channel in an environment that normally supports that channel's function.
| Koyrakh, Lev; Roman, Maria I; Brinkmann, Volker et al. (2005) The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I. Am J Transplant 5:529-36 |
| Koyrakh, Lev; Lujan, Rafael; Colon, Jose et al. (2005) Molecular and cellular diversity of neuronal G-protein-gated potassium channels. J Neurosci 25:11468-78 |
