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.
Shen
W X
WX
Department of Neurobiology, University of Pittsburgh School of Medicine, E1440 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Horn
J P
JP
D000818:Animals; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D011892:Rana catesbeiana; D009435:Synaptic Transmission / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D018733:Nicotinic Antagonists; D008464:Mecamylamine