Block of the ryanodine receptor channel by neomycin is relieved at high holding potentials.

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.