Massachusetts General Hospital

BiographyMy research focuses on the molecular mechanism by which volatile anesthetics potentiate TASK tandem pore potassium channel function and the role of these pH- and hypoxia-sensitive channels in regulation of breathing. We use an Ussing chamber electrophysiologic system to study these channels and employ a number of molecular techniques, including molecular co-expression, site-directed mutagenesis, and RNA interference. We also use whole-body plethysmography to study breathing.

Research

Research Areas

Anesthetic Mechanisms and Pharmacology,  Respiratory Physiology/Regulation of Breathing

Description of Research My research focus is TASK tandem pore potassium channels.  I am interested in the role of TASK channels in volatile anesthetic mechanisms and regulation of breathing and blood pressure by the carotid bodies.  TASK potassium channel function is activated by volatile anesthetics and may contribute to volatile anesthetic-induced loss of consciousness and immobility.  I have optimized an Ussing chamber electrophysiology rig for study of TASK function and, combined with site-directed mutagenesis and other molecular biology techniques, am studying the details of their regulation by volatiles.  The carotid bodies are essential for the protective breathing and hemodynamic response to hypoxia.  Carotid body function is, unfortunately, inhibited by most anesthetic drugs and likely contributes to their very low therapeutic index.  TASK channels are expressed in the carotid body and may have a role in carotid body chemosensing (oxygen and acidic pH sensing).  I am undertaking studies to determine the role of TASK channels in carotid body inhibition by volatile anesthetics and am developing pharmacologic strategies to reverse this inhibition.  

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