DIFFERENTIAL BLOCK OF NICOTINIC SYNAPSES ON B-NEURONS VERSUS C-NEURONS IN SYMPATHETIC-GANGLIA OF FROG BY ALPHA-CONOTOXINS MII AND IMI

1 The effects of two new acetylcholine receptor antagonists, alpha-con otoxin MII and alpha-conotoxin ImI, on nicotinic synaptic transmission in the 10th paravertebral sympathetic ganglion of the leopard frog (R ana pipiens) were examined. The preganglionic nerve was electrically s timulated (at low frequency, less than or equal to 1 min(-1), to avoid use-dependent changes) while compound action potentials of B and C ne urones were monitored from the postganglionic nerve. 2 alpha-Conotoxin s MII and ImI, at low micromolar concentrations, reversibly blocked bo th B and C waves. alpha-Conotoxin MII blocked the C wave more effectiv ely than the B wave, whereas the potency of alpha-conotoxin ImI was op posite that of MII. The observation that nicotinic antagonists can dif ferentially block synaptic transmission of B versus C neurones with op posite selectivities strongly suggests that these neurones possess dis tinct nicotinic receptors. 3 In addition to fast and slow B waves desc ribed by others, C waves with two temporally distinguishable component s were present in our recordings. Each alpha-conotoxin affected fast a nd slow B waves similarly. Likewise, toxins did not discriminate betwe en the two components of C waves. This suggests that all neurones with in each major class (B or C) may have the same nicotinic receptors.4 S ynthetic forms of alpha-conotoxins MII and ImI were used in the presen t study. Their ease of synthesis and their specificities should make t hese toxins useful probes to investigate the various subtypes of neuro nal nicotinic acetylcholine receptors.