STRYCHNINE - A POTENT COMPETITIVE ANTAGONIST OF ALPHA-BUNGAROTOXIN-SENSITIVE NICOTINIC ACETYLCHOLINE-RECEPTORS IN RAT HIPPOCAMPAL-NEURONS

In our study, evidence is provided that strychnine, a competitive anta gonist at glycine-gated Cl- channels, is also a potent competitive ant agonist at native alpha-7-containing, alpha-bungarotoxin-sensitive nic otinic acetylcholine receptor (nAChRs). To address the effects of stry chnine on two types of nicotinic responses, the whole-cell mode of the patch-clamp technique was applied to rat hippocampal neurons in cultu re. Type IA and type II nicotinic currents evoked by acetylcholine (AC h) were inhibited by strychnine in a concentration-dependent manner wi th IC(50)s of 1.2 and 38 mu M, respectively. Strychnine (2 mu M) decre ased the peak amplitude of the alpha-bungarotoxin-sensitive type IA cu rrent in a voltage-independent manner and prolonged the decay phase of this current. The concentration-response curve for ACh in evoking typ e IA current showed a parallel shift to the right in the presence of s trychnine (2 mu M); the EC50 for ACh was increased from 0.4 to 0.8 mM. These findings suggest that strychnine acts as a competitive antagoni st of ACh at the alpha 7 nAChRs that subserve type IA current. In cont rast, the inhibition by strychnine of type II current was strongly vol tage dependent, and the decay phase of this current was markedly accel erated by the toxin, suggesting an open-channel blockade by strychnine of the alpha 4 beta 2 nAChRs subserving type II currents. Preexposure of the neurons to strychnine enhanced its ability to decrease the pea k amplitude of type II currents, indicating that the toxin may also ac t on alpha 4 beta 2 nAChR channels that are not open. It is concluded that strychnine is a potent competitive antagonist of ACh at neuronal alpha 7 nAChRs and a noncompetitive antagonist at the alpha 4 beta 2 n AChR.