L-type voltage activated calcium (Ca) channels are heteromultimeric proteins composed of a pore-forming alpha1 subunit and accessory subunits known as Beta, alpha2, delta, and gamma. Though electrophysiological studies have demonstrated that these accessory subunits are critical determinants of channel properties, the biochemical and molecular events underlying the interaction of these subunits is largely unknown. The proposed studies will address the hypothesis that multiple interactions are involved in the modulation of channel properties by accessory subunits. The two-hybrid system will be used to identify domains involved in protein-protein interactions. Subsequently, the functional significance of these interactions will be assessed in a mammalian cell expression system where a variety of immunological, pharmacological, and electrophysiological approaches can be used to evaluate channel properties and channel function. This multidisciplinary approach will lend further understanding into the mechanisms underlying Ca channel subunit associations, and consequently, channel function. Clinically, the elucidation of interacting domain will aid searches to identify novel pharmacological targets whereby Ca channels may be therapeutically manipulated, which would be extremely beneficial given the wide spectrum of disorders, particularly in the CNS, which are associated with changes in Ca homeostasis.
| Eavani, Harini; Habes, Mohamad; Satterthwaite, Theodore D et al. (2018) Heterogeneity of structural and functional imaging patterns of advanced brain aging revealed via machine learning methods. Neurobiol Aging 71:41-50 |
| Sharma, Anup; Satterthwaite, Theodore D; Vandekar, Lillie et al. (2016) Divergent relationship of depression severity to social reward responses among patients with bipolar versus unipolar depression. Psychiatry Res Neuroimaging 254:18-25 |
| Meyers, M B; Puri, T S; Chien, A J et al. (1998) Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca2+ channels. J Biol Chem 273:18930-5 |
| Chien, A J; Hosey, M M (1998) Post-translational modifications of beta subunits of voltage-dependent calcium channels. J Bioenerg Biomembr 30:377-86 |
| Chien, A J; Carr, K M; Shirokov, R E et al. (1996) Identification of palmitoylation sites within the L-type calcium channel beta2a subunit and effects on channel function. J Biol Chem 271:26465-8 |
