Mecamylamine selectively blocks nicotinic receptors on vasomotor sympathetic C neurons

Abstract

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.