Elsevier

Behavioural Brain Research

Volume 73, Issues 1–2, 15 December 1995, Pages 269-272
Behavioural Brain Research

Desensitization of 5-HT3 receptors expressed in Xenopus oocytes: dependence on voltage and primary structure

https://doi.org/10.1016/0166-4328(96)00110-6Get rights and content

Abstract

The wild-type and a mutant 5-HT3 receptor were expressed in Xenopus oocytes to further explore how the rate of onset of desensitization of the 5-HT3 receptor was dependent on membrane voltage and primary structure of the channel. The rapid application of serotonin (5-HT; 50 μM) in a Ca2+-containing (1.8 mM) bathing solution elicited inward currents that decayed rapidly and with a biphasic time course in most cases. For oocytes expressing the wild-type 5-HT3 receptor and held at a potential of −90 mV, the value of the fast time constant of decay (τfast was 0.79 ± 0.3 s (n = 7), while τslow was 16 ± 3 s; the area of the decay phase contributed by τfast (i.e., Afast) was 50 ± 4% and Aslow was 38 ± 5%, with a remainder (i.e., non-desensitizing component) of 12%. The kinetics of the decay phase were strongly voltage-dependent. At a holding potential of −30 mV, the desensitization decay phase was now monophasic, with a time constant of 14.0 ± 3.1 s (n = 4). Mutating the leucine at position 286 of the wild-type 5-HT3 receptor to threonine (i.e., mutant L286T) resulted in desensitization kinetics that were biphasic at all membrane potentials tested and with a rate of decay that was not voltage dependent. Therefore, desensitization is a multifaceted and complex process, whose rate of onset depends in part to membrane voltage and primary structure of the ion channel.

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Cited by (7)

  • Co-expression of the 5-HT<inf>3B</inf> serotonin receptor subunit alters the biophysics of the 5-HT<inf>3</inf> receptor

    2003, Biophysical Journal
    Citation Excerpt :

    Nevertheless, recent studies have started to unravel some of the molecular steps of desensitization of ionotropic glutamate receptors (Sun et al., 2002). Desensitization kinetics of 5-HT3 receptors depend on, e.g., receptor subunit amino acid sequence, extracellular calcium concentration (Gunthorpe et al., 2000; Lobitz et al., 2001; Yakel, 1996; Yakel et al., 1993), and the developmental state of cells (Shao et al., 1991). The present study investigates the effect of co-expressed 5-HT3B receptor subunits on 5-HT3 receptor activation, desensitization, and recovery from desensitization.

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