LABORATORY FOCUS

The focus of this laboratory is to study the molecular mechanisms related to the sensory cells involved in hearing and balance. These cells are called hair cells. Genetic diseases involving hair cells lead to deafness, imbalance and falls. Non-physiological stimulation of these cells causes vertigo in aviators and space sickness in astronauts and cosmonauts. Hair cells communicate with the outside environment by ion channels in their cell wall. Mutations in the polypeptides that make up ion channels lead to rare but serious maladies including irregular heart beat, muscle spasms, body deformities,  limb paralysis and migraine headaches. Diseases caused by dysfunction of ion channels are called channelopathies.

We measure with special amplifiers minute electrical currents (10^-12 amperes) caused by ions such as potassium and calcium passing through the pores of the ion channels. We also determine sequences of amino acids that make up the ion channel proteins.  There are up to 8 different ion channels on a single small hair cell (20 microns X 10 microns). Each ion channel has a special role in helping the inside of the cell communicate with the outside fluids that surround the hair cell. Part of the ion channel protein is on the outside of the cell so we look for places where we can attach or bind drugs to change the ion channel for therapeutic purposes. To this end, recently we have become interested in studying other proteins that modify or modulate the ion channel’s ability to pass ions. One such molecule is acetylcholine which is coupled to ion channels by a receptor and a special protein called a G-protein. We are actively studying muscarinic receptors which are coupled to an ion channel (inward rectifier channel) that causes the cell’s membrane to be negative. Several of the ion channels found in the cell membrane of hair cells can be modulated by acetylcholine or like molecules (agonists). Two of these ion channels are the inward rectifier potassium channel (Kir family) and an outward rectifier potassium channel (KCNQ family).We are actively studying what causes these ion channels to open and close.

Finally we use contemporary techniques to assist us in these studies. These techniques include genomic methods such as bioinformatics, cloning, sequencing, mutation and expression. We use proteomics methods including electrophoresis, blotting, immunoprecipitation, immunohistochemistry and immunocytochemistry. We use electrophysiological methods including whole cell and single channel electrophysiology.

Our long term goal is to help the hearing and balance of the sick and elderly!!!