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Photosensitizer-generated reactive oxygen speeds activation
of the slow cardiac delayed rectifier potassium current
Tarr, Merrill1, Frolov, Andrey2
and Valenzeno, Dennis1
University of Kansas Medical Center, Kansas City, KS1
Washington University School of Medicine, St. Louis, MO2
Abstract-
We have demonstrated previously that the delayed rectifier potassium
current (IK) is blocked by rose bengal-induced photosensitization
in frog cardiac cells. We now report that such photosensitization also
alters the time course of activation of this current, i.e. its
activation kinetics. The remaining unblocked current has a less sigmoid
activation time course than normal. We also demonstrate that the membrane
potential during photomodification influences the alteration of the
activation kinetics. Photosensitization at positive membrane potentials
is more effective at altering activation kinetics than is photosensitization
at negative membrane potentials. This contrasts with our previous finding
that IK block is more sensitive to photosensitization at
negative than positive membrane potentials. Similar to the so-called
slow delayed rectifier potassium current (IKs) in mammalian
heart, the frog IK activates very slowly (over many seconds).
This similarity of activation time course, as well as similarities regarding
drug sensitivity, suggests that the frog IK (like the mammalian
IKs) relates to the potassium channel composed of the KvLQT1
protein subunit associated with the nonchannel, regulatory MinK protein.
Accordingly, we discuss how our results may relate to photosensitization-induced
alterations in and/or disruption of MinK protein regulation of this
type of potassium channel. [Supported by a Grant-in-Aid from the American
Heart Association, Kansas Affiliate.]
Keywords: rose bengal, potassium current, activation kinetics,
frog cardiac cells
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