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Optical imaging utilizing voltage-sensitive dyes has become
a powerful tool for the analysis of cardiac excitation. Until recently, it has
been primarily used for fluorescence surface recordings, where only the
subsurface layers beneath the epicardial surface were shown to contribute to
the optical signal. However, the myocardial wall can be up to 1 cm thick and
imaging of the heart’s electrical activity throughout the thickness of the
ventricular muscle would greatly add to the understanding of the mechanisms
underlying cardiac arrhythmias. |
Voltage-sensitive dyes (e.g. di-4-ANEPPS) have been widely
and successfully used as probes for mapping membrane potential changes in
cardiac cells and tissues for over 25 years. However, their utility has been
somewhat limited because their excitation wavelengths have been restricted to
the 450-550 nm range. We are developing near-infrared (NIR) membrane voltage
probes because absorption and scattering in cardiac tissue are weaker for NIR
light. In optical mapping applications,
reduced absorption and scattering result in improved recordings from deeper
tissue layers. The new NIR voltage-sensitive dyes are being developed in close
collaboration with Dr. L.Loew‘s group. |
Proper expression of ion channel genes is
responsible for maintaining the electrical properties of cardiac tissue. Ion channel expression changes across
different areas of the heart. These
changes allow myocytes to specialize in signal propagation, contraction, or
pace-making. Further alterations in ion
channel transcriptional expression are associated with diseases such as atrial
fibrillation. We study the regulation of
ion channel gene expression at the transcriptional level using bioinformatic
data mining approaches to analyze the core promoter of ion channel genes. Our effexpression patterns may lead to novel
drug targets in treating cardiovasorts to predict ion channel cular arrhythmias
and disease. |