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Journal of Biomedical Research | Volume: 29
November 19-20, 2018 | Paris, France
Molecular Biology, Tissue Science and Regenerative Medicine
International Conference on
Joint Event
&
4
th
World Heart Congress
Structural and functional insights into cholesterol regulation of k+ channels in vasculature and heart
Irena Levitan
University of Illinois at Chicago, USA
O
ur research focuses on the mechanisms that underlie
cholesterol regulation of ion channels with particular focus
on inwardly rectifying K+ channels (Kir), which is responsible for
regulating membrane potential and excitability in a variety of
cells types including cardiomyocytes, smooth muscle cells and
endothelial cells. We have found that an increase inmembrane
cholesterol paradoxically has opposite effects on two types of
Kir channels expressed in cardiomyocytes, it simultaneously
suppressed the activity of Kir2.1 channels responsible for the
basal Kir activity and enhances the activity of cardiac KACh
channels which plays a key role in the control of the heart rate.
We propose that the loss of basal Kir activity together with
enhanced activity of KACh should result in destabilization of the
heart rate control and development of arrhythmias. In terms of
the molecular mechanisms of cholesterol-induced regulation
of the channels, we discovered that the channels interact
with an ensemble of cholesterol molecules and identified
novel cholesterol binding sites that are specific for open and
closed states of the channels. We also show that increase in
membrane cholesterol
in vitro
and in vivo suppresses flow
sensitivity of Kir2.1 channels, a hallmark of they function in
vascular endothelium.
Speaker Biography
Irena Levitan, is a professor of Medicine and adjunct professor of Bioengineering
at the University of Illinois at Chicago. Her current research focuses on cholesterol
regulation of ion channels and cellular biomechanics. Levitan’s group provided the
first comprehensive structural insights into cholesterol regulation of K+ channels and
the cross-talk between cholesterol and other regulators of these channels. She was
named a Guyton distinguished lecturer by the Association of chairs of Departments of
Physiology for her quantitative and biophysical work on cholesterol modulation of ion
channels and how this can affect integrated organ function. She is an author of more
than 70 publications and a leading editor of Cholesterol regulation of Ion Channels and
Receptors (Wiley, 2012) and Vascular Ion Channels (Springer, 2016).
e:
levitan@uic.eduIrena Levitan, Molecular Biology & Heart Congress 2018, Volume 29
DOI: 10.4066/biomedicalresearch-C8-022