Cytoplasmic BK
The invention relates to a method of modulating neuronal function by modulating the cytoplasmic level in a neuron of an intron-containing mRNA. The methods are useful in diagnostic, research and therapeutic applications.
1. A method of decreasing the excitability of a neuron, said method comprising administering to the neuron an siRNA molecule specific for intron-containing KCNMA1 mRNA, wherein the administration of the siRNA molecule specific for intron-containing KNCMA1 mRNA decreases the cytoplasmic level of intron-containing KCNMA1 mRNA in the neuron, wherein the decrease in the cytoplasmic level of intron-containing KCNMA1 mRNA causes a decrease in the excitability of the neuron.
2. The method of claim 1 , wherein said intron-containing KCNMA1 mRNA comprises intron 16.
3. The method of claim 2 , wherein said intron 16-containing KCNMA1 mRNA further comprises exon 17 spliced directly to exon 18.
4. The method of claim 1 , wherein decreasing the cytoplasmic level of intron-containing KCNMA1 mRNA causes a change in distribution of BK Ca channels in the neuron.
5. A method of modulating the function of a neuron, said method comprising
administering to the neuron an siRNA molecule specific for intron-containing KCNMA1 mRNA, wherein the administration of the siRNA molecule specific for intron-containing KNCMA1 mRNA decreases the cytoplasmic level of intron-containing KCNMA1 mRNA in the neuron,
wherein the decrease in the cytoplasmic level of intron-containing KCNMA1 mRNA modulates the function of the neuron.
6. The method of claim 5 , wherein the intron-containing KCNMA1 mRNA is dendritically targeted.
7. The method of claim 1 , wherein the siRNA molecule specific for intron-containing KCNMA1 mRNA comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34.
8. The method of claim 5 wherein the siRNA molecule specific for intron-containing KCNMA1 mRNA comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34.