Patent ID: 7049083

Claim:
A method for identifying compounds which inhibit N-type inactivation of a voltage-gated ion channel, comprising: a) administering a compound to a modified host cell comprising: i) a first hybrid protein comprising a DNA-binding domain of a transcriptional activator in polypeptide linkage to either 1) an S4–S5 cytoplasmic loop of an α-subunit of a voltage-gated ion channel; or 2) an amino-terminal inactivation region of an ion channel protein; ii) a second hybrid protein comprising an activation domain of a transcriptional activator in polypeptide linkage to said S4–S5 cytoplasmic loop if said DNA-binding domain is in polypeptide linkage to said amino-terminal inactivation region or to said amino-terminal inactivation region if said DNA-binding domain is in polypeptide linkage to said S4–S5 cytoplasmic loop; and iii) a reporter gene whose transcription is dependent upon the first hybrid protein and the second hybrid protein being bound to each other, thereby reconstituting a transcriptional activator; b) incubating the modified host cell for a suitable period; c) determining whether the administration of the compound inhibits expression of the reporter gene; and d) identifying a compound which inhibits expression of the reporter gene as an inhibitor of N-type inactivation of said voltage-gated ion channel.