SINGLE AMINO-ACID SUBSTITUTION AFFECTS DESENSITIZATION OF THE 5-HYDROXYTRYPTAMINE TYPE-3 RECEPTOR EXPRESSED IN XENOPUS-OOCYTES

5-Hydroxytryptamine type 3 receptors were expressed in Xenopus oocytes from a cloned cDNA. The peak inward current evoked by 5-hydroxytrypta mine (30 muM) was linearly related to the holding potential (-100 to 20 mV) and reversed near 0 mV. The inward current (at -60 mV) declined during the continued presence of 5-hydroxytryptamine with a half-time of about 2 s; this desensitization was 20 times slower in calcium-fre e solution. Desensitization was markedly different in channels in whic h Leu286 was changed by site-directed mutagenesis; this residue is tho ught to lie near the middle of the M2 segment. Desensitization was fas ter with Phe, Tyr, or Ala in this position and slower with Thr. Phe an d Thr substitutions in the equivalent position of the nicotinic acetyl choline receptor have similar effects on desensitization, suggesting t hat the underlying conformational change might be common to ligand-gat ed channels.