Aminoglycoside Effects on Voltage-Sensitive Calcium Channels and Neurotoxicity

To the Editor: Since ototoxicity and neuromuscular toxicity of aminoglycoside antibiotics are reversed by calcium,^1,2 and presynaptic events appear to be involved in aminoglycoside-induced neuromuscular blockade,^3,4 we suspected a role for voltage-sensitive calcium channels in aminoglycoside neurotoxicity. Among the several subtypes of those channels, the N-channel is predominantly involved in neurotransmitter release.^{5 6 7} We investigated the influences of therapeutic concentrations of aminoglycosides on N-channels monitored by either ⁴⁵Ca²⁺ uptake or binding of the calcium-channel toxin [¹²⁵I]omega-conotoxin GV IA, which predominantly labels N-channels in neuronal membranes.⁸ Aminoglycosides inhibit brain neuronal and sympathetic-ganglia–membrane binding of [¹²⁵I]conotoxin, and relative potencies correlate closely…, No extract is available for articles shorter than 400 words.