The primary goal is to determine the molecular structure of the dihydropyrdine-sensitive calcium channel from skeletal muscle. Voltage-dependent calcium channels will be purified from transverse tubule membranes using labelled dihydropyridines as probes for the solubilized channel. The isolated polypeptide subunits will be reconstituted into planar lipid bilayers and lipid vesicles in order to compare the function of the purified channel protein with the function of calcium channels in intact cell membranes. Three major questions will be addressed: (1) What is the minimum subunit composition required for a completely functional calcium channel? (2) Is there more than one type of dihydropyridine-sensitive calcium channel in skeletal muscle? (3) How is calcium channel function affected by phosphorylation? Using purified reconstituted calcium channels, it will be possible to correlate specific modifications of the channel structure with specific effects on channel function. The long-term goals are to understand the biochemical structure underlying voltage-dependent calcium channel function, and to develop biochemical probes which can be used to define the structural differences among different types of calcium channel.
| Kim, K C; Caswell, A H; Talvenheimo, J A et al. (1990) Isolation of a terminal cisterna protein which may link the dihydropyridine receptor to the junctional foot protein in skeletal muscle. Biochemistry 29:9281-9 |
| Brandt, N R; Caswell, A H; Wen, S R et al. (1990) Molecular interactions of the junctional foot protein and dihydropyridine receptor in skeletal muscle triads. J Membr Biol 113:237-51 |
| Talvenheimo, J A; Worley 3rd, J F; Nelson, M T (1987) Heterogeneity of calcium channels from a purified dihydropyridine receptor preparation. Biophys J 52:891-9 |
