The voltage-gated KCNQ1-5 (Kv7.1-7.5) family of potassium channels plays a significant role in controlling the excitability of cells comprising the heart, skeletal muscle, the nervous system, and cochlea. Impairment in the normal gating activities as the result of mutations in the channel itself causes several human diseases including cardiac arrhythmia, epilepsy, and deafness. In order to develop novel therapeutic strategies for treating patients suffering from these disease causing mutations, we first need to understand the mechanisms governing KCNQ regulation. Calmodulin (CaM) through its interaction with IQ-domains located in the C-terminus of the channel is known to be important for channel expression, trafficking, and gating. Members of the CaM-like Ca2+ binding proteins (CaBPs) have been identified as CaM antagonist as they compete with CaM for binding to IQ-domains in the C-terminus of Ca2+ channels. My proposed work will provide valuable new insight into how CaBP1, a member of the CaM-like Ca2+ binding proteins, modulates KCNQ channel activity.
Mutations that impair normal acting activities of KCNQ potassium channels cause cardiac arrhythmia, epilepsy, and deafness. In order to develop novel therapeutic strategies for treating these disease-causing mutations, we first need to understand the mechanisms governing KCNQ regulation. My proposed work will provide new insights into how CaBP1, a Ca2+ binding protein highly expressed in the inner ear, modulates KCNQ channel activity and the contribution of these channels to processes underlying normal hearing.
