Methods for identifying modulators of N-type ion channel inactivation

A modified host cell comprising:

• a first hybrid protein comprising an intracellular receptor region of an α-subunit of a voltage-gated ion channel in polypeptide linkage to a first peptide of a peptide binding pair;
• and
• a second hybrid protein comprising an amino-terminal inactivation region of an ion channel protein in polypeptide linkage to a second peptide of the peptide binding pair;
• wherein binding interaction between the first peptide and the second peptide in the modified host cell causes activation of a signal transduction pathway in said modified host cell.

A polynucleotide encoding a DNA-binding domain or an activation domain of a transcriptional activator and comprising a nucleotide sequence selected from the group consisting of:

• (a) the nucleotide sequence of SEQ ID NO:
• 3;
• (b) the nucleotide sequence of SEQ ID NO:
• 4;
• (c) a nucleotide sequence which is at least 90% identical to the nucleic acid of (a) or (b) and which encodes a peptide that is capable of binding to an amino-terminal inactivation region of an ion channel protein;
• and
• (d) a nucleotide sequence which is degenerate as a result of the genetic code to a nucleic acid defined in (a) or (b) and which encodes a peptide that is capable of binding to an amino-terminal inactivation region of an ion channel protein.

A polynucleotide encoding a DNA-binding domain or an activation domain of a transcriptional activator and comprising a nucleotide sequence selected from the group consisting of:

• (a) the nucleotide sequence of SEQ ID NO:
• 7;
• (b) the nucleotide sequence of SEQ ID NO:
• 8;
• (c) a nucleic acid molecule which is at least 80% identical to the nucleic acid of (a) or (b) and which encodes a peptide that is capable of binding to an intracellular receptor region of an α-subunit of a voltage-gated ion channel;
• and
• (d) a nucleic acid molecule which is degenerate as a result of the genetic code to a nucleic acid defined in (a) or (b) and which encodes a peptide that is capable of binding to an intracellular receptor region of an α-subunit of a voltage-gated ion channel.