Block of the ryanodine receptor channel by neomycin is relieved at high holding potentials
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Updated: Oct 2, 2026

Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
1Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College of Science, Technology & Medicine, London SW3 6LY, United Kingdom.
Abstract:
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.
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