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Anatoli
N. Lopatin, Ph.D.
~Assistant Professor of Molecular & Integrative Physiology
Ph.D.,
Research Center of Molecular Diagnostics, Moscow, Russia,
1990
7812
Med. Sci. II
(734) 615-8903
alopatin@umich.edu
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Current Research:
Inwardly rectifying
potassium, or Kir, channels are critical regulators of cellular
excitability. They function like electronic diodes to stabilize
cells restating potential and to regulate potassium balance. The
mechanism of their unusual behavior to conduct ions readily only
in one direction, a phenomenon called inward rectification, was
largely unknown until it has been recently discovered that small
ubiquitous molecules called polyamines (putrescine, spermidine and
spermine) are the sole reason for this 'anomalous' effect. One of
the goals of our laboratory is to understand on the molecular level
how polyamines interact with the channel protein to cause inward
rectification. To approach this problem we utilize electrophysiological,
molecular biological and computer modeling techniques. Besides attacking
the biophysical part of the phenomenon of rectification we are also
interested in the regulation of cellular excitability by genetic
manipulation of both Kir channels and polyamines in experimental
animals. The heart is one of the major organs where intracellular
polyamines cause the strongest rectification of potassium channels.
We are now producing and characterizing transgenic mice with genetically
altered polyamine biosynthesis and Kir channels to understand in
more detail the physiological role of these channels in the function
of the heart. This approach includes molecular biological design
of mutated enzymes of polyamine biosynthesis and potassium channels,
their targeted expression in the heart and studying the effects
of genetic manipulation on the single cell level using patch-clamp
technology and on the level of isolated heart and whole animal.
Selected
Publications:
Lopatin, A.N., Makhina, E.N. and C.G. Nichols (1994): Potassium
channel block by cytoplasmic polyamines as the mechanism of intrinsic
rectification. Nature 372: 366-369.
Lopatin, A.N., and C.G. Nichols (1995) The mechanism of
inward rectification of potassium channels. Journal of General Physiology
106: 923-955.
Lopatin, A.N. and C.G. Nichols. Inward Rectifiers in the
Heart: An update on IK1. Journal of Molecular and Cellular Cardiology,
2001, 33(4): 625-638.
McLerie, M. and Lopatin A.N. Dominant Negative Suppression
Of Ik1 In The Mouse Heart Leads To Altered Cardiac Excitability.
Journal of Molecular and Cellular Cardiology, 2003, 35(4): 367-78.
Li J, McLerie M and Lopatin A.N. Transgenic Up-Regulation
of IK1 in The Mouse Heart Leads to Multiple Abnormalities of Cardiac
Excitability. American Journal of Physiology. Heart and Circulation
Physiology. 2004 Jul 22 [Epub ahead of print].
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