We are interested in how ion channels control the excitability of neurons and how this influences the activity of neural circuits. Abnormal hyperexcitability is a defining feature of clinically significant diseases such as epilepsy. Our understanding of these diseases currently is limited by gaps in our understanding of how neuronal excitability is controlled. Voltage-gated K+ currents that activate below the threshold for action potential initiation can have a profound influence on excitability, but the molecular basis and modulation of these currents is still not well understood. We have undertaken a major effort to dissect the physiological roles of these currents using both genetic and pharmacologic approaches. We recently have found that the K+ channel Kv12.2 accounts for a significant fraction of sub-threshold K+ current in hippocampal neurons. Kv12.2 has a strong influence on firing threshold and loss of the Kv12.2 current leads to epilepsy. We currently are investigating Kv12.2 as a potential new therapeutic target for seizure control. We are expanding our work to examine the roles of Kv12 channels in sensory perception and to identify other key components of sub-threshold K+ currents in central neurons.
