ABSTRACT
Potassium channel proteins are involved in many aspects of human physiology. Small
conductance calcium-activated potassium channels (SK channels) are voltage-independent and
widely expressed in excitable cells. Our laboratory determined that expression of kcnn1, which
encodes the SK1 channel, is upregulated after spinal cord injury in zebrafish. Our preliminary data
using a potassium channel inhibitor, 4-aminopyridine, demonstrates that inhibition enhances
swim recovery in zebrafish suggesting modulation of SK channels may be potentially useful as a
therapeutic approach for SCI. The broad, long-term objective of the project is to determine the
role of SK1 in recovery from spinal cord injury (SCI). To achieve this goal, we will first construct
knockout and transgenic zebrafish for both paralogs of the SK1 channel. We will determine
whether these lines properly develop a spinal cord and use optogenetic techniques to
spatiotemporally control kcnn1 expression after SCI. Second, we will use pharmacological
approaches to determine how modulation of SK channels mediates functional recovery after SCI.
These studies will clarify the role of SK channels and specifically SK1 in recovery from SCI. We
expect that the developed lines will be useful to study additional neurological pathologies and
facilitate drug screening to identify new therapeutics for neurodegenerative diseases.