FUNCTIONAL-HETEROGENEITY OF NICOTINIC RECEPTORS IN THE AVIAN LATERAL SPIRIFORM NUCLEUS DETECTED WITH TRIMETHAPHAN

We have examined an excitatory response mediated by nicotinic acetylcholine receptors located on the somata and/or dendrites of chick lateral spiriform neurons. On the basis of pharmacological and anatomical studies, these receptors belong to a subgroup of nicotinic receptors termed high affinity nicotine receptors, because they exhibit a high affinity for nicotinic agonists but little or no sensitivity to alpha- or kappa-bungarotoxin. We now report physiological evidence that high affinity nicotine receptors in the lateral spiriform nucleus are heterogeneous. Intracellular recording in brain slices was used to examine the pharmacological characteristics of nicotinic responses in individual lateral spiriform neurons. Nicotinic responses to brief applications of carbachol were inhibited by trimethaphan, dihydro-beta-erythroidine, or d-tubocurarine. Trimethaphan was unusual, in that a wide range of concentrations (less than or equal to 50 mu M to > 500 mu M) were required to block this nicotinic response in different neurons. To quantitate the inhibition observed with trimethaphan and dihydro-beta-erythroidine, dose-response curves were generated in superfusion studies using a wide range of concentrations of both agonist (3-3000 mu M carbachol in the presence of 1 mu M atropine and 0.25 mu M tetrodotoxin) and antagonists (10-500 mu M trimethaphan or 0.1-3 mu M dihydro-beta-erythroidine). The data yielded an EC(50) of 25 +/- 5 mu M for carbachol, with a Hill coefficient of 1.4 +/- 0.1 (mean +/- standard error; n = 8). In the case of dihydro-beta-erythroidine, a narrow range of K-i values was obtained (0.09-0.16 mu M; n = 5). In contrast, K-i values for trimethaphan varied over a 15-fold concentration range (4-66 mu M; n = 17), demonstrating that trimethaphan showed selectivity for different receptor subtypes found in the lateral spiriform nucleus. For both antagonists, the data indicate a competitive mode of inhibition.