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.
Mead
Fiona
F
Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College of Science, Technology & Medicine, London SW3 6LY, United Kingdom.
Williams
Alan J
AJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D055592:Biophysical Phenomena; D001703:Biophysics; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007700:Kinetics; D008051:Lipid Bilayers; D008958:Models, Molecular; D009355:Neomycin / Q000737:chemistry / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012756:Sheep; D013997:Time Factors
D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D019837:Ryanodine Receptor Calcium Release Channel; D009355:Neomycin; D011188:Potassium