Cellular Neurophysiology Laboratory

A typical CA1 hippocampal pyramidal neuron showing its extensively branched apical dendrites. HCN channels are predominately localized to the dendrites where they strongly influence the integration of synaptic input. Studying HCN channel behavior requires dendritic patch clamp recording techniques.

HCN channels, phosphorylation signaling, antiepileptic drugs, and epilepsy

The Cellular Neurophysiology Laboratory at the University of Washington is based at Harborview Medical Center, is part of the Neurology Department and Regional Epilepsy Center, and is affiliated with the Physiology and Biophysics department. Our research is focused on the molecular causes of epilepsy, with the goal of discovering novel targets for epilepsy therapeutics. We were one of the first to characterize the role of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in epilepsy, and identify these ion channels as the target of antiepileptic drugs. HCN channels are voltage-gated ion channels in hippocampal pyramidal neuron dendrites that inhibit pyramidal neuron excitability. HCN channel expression and function is lost early in the development of epilepsy, so we’re interested in understanding the molecular mechanisms of HCN channel regulation and how they may be targeted in novel therapeutic approaches to the prevention and treatment of epilepsy.

We have recently identified a phosphorylation signaling pathway that is hyperactivated in epilepsy (c-Jun N-terminal kinase or JNK) and are investigating how this pathway may contribute to the neurodegeneration seen with uncontrolled seizures.

We are also interested in how antiepileptic drugs work and how their use may be optimized for patients with refractory epilepsy. By studying clinical databases of epilepsy treatment, including online seizure diaries, we have discovered drug regimens that are particularly effective in this difficult-to-treat patient population.

The techniques in use in the lab include: whole-cell and cell-attached patch clamp recording in hippocampal pyramidal neuron dendrites using IR and fluorescence imaging of neurons in the brain slice preparation; animal models of acquired temporal lobe epilepsy; biochemical techniques including mass spectrometry; and informatic approaches to comparative effectiveness research.

We’re always looking for individuals interested in our research who would like to join our lab. Feel free to contact us.