Figure 4

<p>(A) Rundown kinetics for chimeras. Representative current traces for human, murine receptors and chimeras showing currents after the first and 26^th application of 5-HT. Records were obtained from the same cell. All chimeras tested produced functional currents upon 5-HT activation. However, the currents through the different receptor chimeras showed a strong variation in kinetics and rundown. (B) Repeated 5-HT-applications (26 applications within 40 min) reduced peak currents (left) and charge (right). Differences were only marginally for peak currents, whereas analysis of charge showed more pronounced variation between all receptor types. (C) Charge variations between the different receptor types displayed a good correlation to kinetic parameters such as desensitization, plateau current and deactivation.</p

Differences in rundown with regard to charge after multiple activation for human, murine and chimeric receptors.

<p>Significant differences (p<0.05, ANOVA) are indicated by black dots.</p

Different receptor chimeras and the respective sequences consisting of human and mouse 5-HT_3A receptor composites.

<p>For clarity, human, murine receptors and chimeras are indicated as a combination of the numbers for the three different sequences, where human sequences are marked in bold and murine sequences are marked in italics. The prefix “H”, “M” and “C” indicates human, murine and chimeric receptors, respectively: human 5-HT₃ receptor = H123, murine 5-HT₃ receptor = M<i>123</i>, chimeric receptors are C1<i>23</i>, C12<i>3</i>, SH1,C<i>12</i>3, C<i>1</i>23 and C1<i>2</i>3.</p

Kinetics of human, murine and chimeric 5-HT_3A receptors after first application of 5-HT for 2 s.

<p>Kinetics of human, murine and chimeric 5-HT_3A receptors after first application of 5-HT for 2 s.</p

Potency of clozapine for human and murine 5-HT_3A receptors and different 5-HT_3A receptor chimeras against peak amplitude.

<p>Significant differences (p<0.05, ANOVA) are indicated by black dots. Comparisons of IC₅₀ for peak amplitude.</p

Differences in rundown with regard to peak amplitude after multiple activation for human, murine and chimeric receptors.

<p>Significant differences (p<0.05, ANOVA) are indicated by black circles.</p

Figure 6

<p>(A, B) 5-HT-induced currents through chimeric receptors. All chimeric receptors were dose-dependently activated by 5-HT. For each dose-response curve values were normalized to the responses induced by 300 µM 5-HT. Dose-response curves for amplitude (A) and charge (B).</p

Amino acid sequence of cloned cDNA encoding the human and mouse 5-HT_3A receptor channel subunit.

<p>Marked in red: mismatches of the amino acid sequence. Marked in green: Restriction sites for BstEII and SgrA1 representing switching points of the chimeric receptors. C-C: Cys-loop. M1–M4 transmembrane segments.</p

5-HT affinity and functional antagonistic properties of the atypical antipsychotic clozapine against H123 and M<i>123</i> currents.

<p>(A) Human and murine 5-HT₃ receptors showed almost identical affinity to 5-HT. (B) Clozapine antagonised 5-HT activated currents through human and murine 5-HT₃ receptors with different potencies, allowing the identification of the structural domains involved in the ligand recognition for clozapine by human/murine chimeras.</p

Potency of serotonin for human, mouse and chimeric 5-HT_3A receptors against peak amplitude.

<p>Significant differences (p<0.05, ANOVA) are indicated by black dots. Comparisons of EC₅₀ for peak amplitude.</p