Mecamylamine selectively blocks nicotinic receptors on vasomotor sympathetic C neurons.

Mecamylamine differentially blocked fast nicotinic transmission in two functional subsets of sympathetic neurons within lumbar paravertebral ganglia of the bullfrog. EC50s for inhibition of postsynaptic compound action potentials were 27.3+/-2.5 microM in the secretomotor B system and 5.7+/-0.7 microM in the vasomotor C system. This 5.2:1 selectivity is 2.6 times greater than observed previously with d-tubocurarine, a nonselective blocker of nicotinic receptors, and it indicates that mecamylamine preferentially interacts with nicotinic receptors on sympathetic C neurons. We tested this by analyzing the effect of mecamylamine upon synaptic currents. In both cell types, the drug produced a qualitatively similar picture of open-channel blockade. It reduced EPSC amplitude, speeded EPSC decay, and became more effective with membrane hyperpolarization and repetitive activity. Despite these similarities, 8 microM mecamylamine reduced EPSC amplitude to a greater extent in C neurons, and the rate constant for drug binding to open channels was 4.4 times greater in B cells, irrespective of membrane potential. This implies that the unblocking rate for mecamylamine is much slower in C cells than B cells, and it shows that the drug recognizes a structural difference between nicotinic receptors on these two populations of sympathetic neurons. Copyright 1998 Elsevier Science B.V.