STRATIFIED ORGANIZATION OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR CHANNEL

MUTATIONS of leucine 247 within the M2 channel domain of the alpha7 neuronal nicotinic receptor, confer electrophysiological and pharmacological properties, which allow one of the desensitized states to become conductive. Here we show that, in Xenopus oocytes, the effects of the mutations were preserved when 1,2-bis(2-aminophenoxy)-ethane N,N,N',N'-tetraacetic acid (BAPTA) was injected in the cytoplasm to block Ca2+- dependent chloride currents, and that in agreement with the proposed interpretation, the ionic currents do not desensitize and rise slowly, in the time-scale of seconds, upon agonist application. Interestingly, similar effects were observed when the two rings (T244, V251) neighbouring L247 on the alpha-helix, but not the more distant ones (S240, L254/255), were mutated, thus supporting the proposal of a functional stratification of the channel domain.