ACTIONS OF NEOMYCIN ON NEURONAL L-TYPE, N-TYPE, AND NON-L/NON-N-TYPE VOLTAGE-SENSITIVE CALCIUM-CHANNEL RESPONSES

The effects of neomycin on neuronal voltage-sensitive calcium channel (VSCC) responses were investigated by evaluating its effects on calcium-dependent neuronal responses that are sensitive and insensitive to the N-type voltage-sensitive calcium channel antagonist omega-conotoxin GVIA and the L-type VSCC antagonist nitrendipine. Chick synaptosomal Ca-45(2+) influx and K+-evoked release of [H-3]norepinephrine from chick cortical brain slices were omega-conotoxin GVIA sensitive and nitrendipine insensitive, suggesting that these responses are mediated predominantly by N-type VSCC. The K+-evoked increase of intracellular calcium in cortical neurons and the K+-evoked release of [H-3]norepinephrine from rat brain cortical slices was partially sensitive to omega-conotoxin GVIA and nitrendipine, suggesting that these responses are mediated by N-, L- and non-L/non-N-type VSCC. Rat synaptosomal Ca-45(2+) influx and the K+-evoked release of [H-3]D-asparate from rat hippocampal slices were completely insensitive to omega-conotoxin GVIA and nitrendipine, suggesting that these responses were mediated predominantly by non-L/non-N-type VSCC. Neomycin caused a concentration-dependent and virtually complete inhibition of all responses parameters, with IC50 values ranging from 90 to 400-mu-M. The results suggest that neomycin is a nonselective inhibitor of neuronal responses mediated by L-, N-, and non-L/non-N-type VSCC.