
Area Of Expertise And Primary Interest
My work is focused on studies of ion channels responsible for the movement of ions like sodium, potassium and calcium across the membrane of cardiac cells. Abnormal function of these ion channels secondary to genetic mutations are responsible for the development of abnormal heart rhythms, known as cardiac arrhythmias. I am also interested in how the function of ion channels changes with development. These studies examine differences the number and function of ion channels in neonate vs. adult hearts as well as differences between the sexes. These studies are critically important in advancing our understanding of cardiac arrhythmias believed to contribute to sudden infant death syndrome (SIDS) and abnormal heart rhythms that place infants and children at risk. Interaction of antiarrhythmic drugs with mutated ion channels is another interest of mine. I am using patch clamp techniques to assess the interaction of the antiarrhythmic drug lidocaine with a mutated sodium channel responsible for the Brugada syndrome. While Class IB antiarrhythmic drugs like lidocaine usually do not unmask or aggravate the Brugada syndrome, we have uncovered a mutation that sensitizes the heart to lidocaine, permitting the drug to induce electrocardiographic changes that unmask the Brugada syndrome. In another study, we have recently shown that compound mutations in SCN5A, the gene that encodes the a subunit of the sodium channel, leads to a more severe dysfunction of the sodium channel. Consistent with our biophysical results, members of the family who inherited the double mutation displayed a more severe clinical phenotype of the Brugada syndrome than the individuals inheriting only a single mutation. Selected PublicationsDevelopmental differences in delayed rectifying outward current in feline ventricular myocytes. Frequency-Dependent Effects of 4-Aminopyridine and Almokalant on Action-Potential Duration of Adult and Neonatal Rabbit Ventricular Muscle. Differences in outward currents between neonatal and adult rabbit ventricular cells. Compound heterozygous mutations P336I and I1660L in the human cardiac sodium channel determine the severity of Brugada syndrome. Identification of two domains involved in the assembly of TRPC channels. A novel mutation in the SCN5A gene associated with arrhythmic storm developing Post-MI. Lidocaine-induced Brugada Syndrome Phenotype Linked to a Novel Mutation and Polymorphism in the Cardiac Sodium Channel. Larger dispersion of sodium current in female dog ventricle as a potential mechanism for gender-specific incidence of cardiac arrhythmias. |
|
|
Medical Research Saves Lives Cardiac Arrhythmias - Cardiovascular Diseases - Sudden Cardiac Arrest ![]() |
|