摘要:
Disclosed are mammalian nucleic acid sequences encoding α1I subunit isoforms of a voltage-gated calcium channel. Specifically disclosed are novel variants of the α1I subunit designated herein as α1I-1 and α1I-2. In other aspects, the disclosure relates to expression vectors which encode the novel subunits of the invention, as well as cells containing such vectors. Antibodies specific for each of the variant subunits are also provided. The nucleic acid sequences of the invention find application, for example, in screening for compounds which modulate the activity of voltage-gated calcium channels and also in diagnostic methods for diagnosing various T-type channel mediated disorders, e.g., epilepsy, cancer, pain, sleep disorders and the autoimmune disease Lambert-Eaton Syndrome. Diagnosing defects in α1I subunit genes of a patient with a neuronal disease such as epilepsy are also included. An additional application of the nucleic acid sequences of the invention is in therapeutic methods of treatment for α1I subunit mediated disorders.
摘要:
Methods of identifying activators and inhibitors of voltage-gated ion channels are provided in which the methods employ cells transfected with a voltage-gated ion channel of interest and a corollary channel to control the membrane potential of the cells by changing extracellular ion concentration. This allows for more convenient, more precise experimental manipulation of these transitions, and, coupled with efficient methods of detecting the result of ion flux through the channels, provides methods that are especially suitable for high throughput screening.