Nucleic acid molecules encoding novel murine low-voltage activated calcium channel proteins, designated-alpha1h, encoded proteins and methods of use thereof
OwnerVictor Uebele, Thomas Connollyinventors
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Abstract
Disclosed herein are novel nucleic acid molecules encoding murine low-voltage activated calcium channel proteins, designated-α1H, encoded proteins, vectors, host cells transformed therewith, as well as pharmaceutical compositions. Methods of using any of the foregoing, e.g., methods for screening for candidate agonists or antagonists utilizing the novel protein isoforms are also disclosed.
Claims20
An isolated nucleic acid molecule comprising a sequence of nucleotides encoding a murine T-type calcium channel α1H subunit selected from the group consisting of:
- (a) a sequence of nucleotides that encodes a murine T-type calcium channel α1H subunit and comprises the sequence of nucleotides set forth in one of SEQ ID NOS:1 or 5;
- (b) a sequence of nucleotides having at least 95% sequence identity or is exactly complementary to the nucleotide sequence set forth in SEQ ID NO:1 or 5, and
- (c) a nucleotide sequence varying from the nucleotide sequence specified in (a) or (b) as a result of degeneracy of the genetic code.
A substantially pure polypeptide comprising an amino acid sequence encoded by the nucleotide sequence as set forth in one of SEQ ID NOS:
- 1 or 5.
A substantially pure polypeptide comprising an amino acid sequence as set forth in one of SEQ ID NOS:
- 2 or 6.
A method for identifying lead compounds for a pharmacological agent useful in the treatment of disease associated with increased or decreased voltage regulated calcium influx mediated by a rat T-type calcium channel comprising:
- (i) providing a cell expressing a rat T-type calcium channel subunit polypeptide designated herein as α1H;
- said calcium channel subunit comprising the amino acid sequence as set forth in one of SEQ ID NOS:
- 2, 4 or 6;
- (ii) contacting the cell with a candidate pharmacological agent under conditions which, in the absence of the candidate pharmacological agent, to thereby cause a first amount of voltage regulated calcium influx into the cell;
- and
- (iii) determining a test amount of voltage regulated calcium influx as a measure of the effect of the lead compounds for a pharmacological agent on the voltage regulated calcium influx mediated by a human T-type calcium channel, wherein (a) the test amount of voltage regulated calcium influx which is less than the first amount indicates that the candidate pharmacological agent is a lead compound for a pharmacological agent which reduces voltage regulated calcium influx and (b) wherein a test amount of voltage regulated calcium influx which is greater than the first amount indicates that the candidate pharmacological agent is a lead compound for a pharmacological agent which increases voltage regulated calcium influx.
Dependencies are inferred from the claim text.