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Biophys J, April 2002, p. 1953-1963, Vol. 82, No. 4
Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College of Science, Technology & Medicine, London SW3 6LY, United Kingdom
In this study we have investigated the actions of the
aminoglycoside antibiotic neomycin on K+ conductance in the
purified sheep cardiac sarcoplasmic reticulum (SR) calcium-release
channel (RyR). Neomycin induces a concentration- and voltage-dependent
partial block from both the cytosolic and luminal faces of the channel.
Blocking parameters for cytosolic and luminal block are markedly
different. Neomycin has a greater affinity for the luminal site of
interaction than the cytosolic site: zero-voltage dissociation
constants (Kb(0)) are respectively 210.20 ± 22.80 and 589.70 ± 184.00 nM for luminal and
cytosolic block. However, neomycin also exhibits voltage-dependent
relief of block at holding potentials >+60 mV when applied to the
cytosolic face and a similar phenomenon may occur with luminal neomycin at high negative holding potentials. These observations indicate that,
under appropriate conditions, neomycin is capable of passing through
the RyR channel.
Biophys J, April 2002, p. 1953-1963, Vol. 82, No. 4
© 2002 by the Biophysical Society 0006-3495/02/04/1953/11 $2.00
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