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Biophys J, April 2002, p. 1953-1963, Vol. 82, No. 4

Block of the Ryanodine Receptor Channel by Neomycin Is Relieved at High Holding Potentials

Fiona Mead and Alan J. Williams

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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