Co-expression of the 5-HT3B serotonin receptor subunit alters the biophysics of the 5-HT3 receptor.
Biophys J
; 84(3): 1720-33, 2003 Mar.
Article
in En
| MEDLINE
| ID: mdl-12609874
ABSTRACT
Homomeric complexes of 5-HT(3A) receptor subunits form a ligand-gated ion channel. This assembly does not fully reproduce the biophysical and pharmacological properties of native 5-HT(3) receptors which might contain the recently cloned 5-HT(3B) receptor subunit. In the present study, heteromeric assemblies containing human 5-HT(3A) and 5-HT(3B) subunits were expressed in HEK 293 cells to detail the functional diversity of 5-HT(3) receptors. We designed patch-clamp experiments with homomeric (5-HT(3A)) and heteromeric (5-HT(3AB)) receptors to emphasize the kinetics of channel activation and desensitization. Co-expression of the 5-HT(3B) receptor subunit reduced the sensitivity for 5-HT (5-HT(3A) receptor EC(50) 3 micro M, Hill coefficient 1.8; 5-HT(3AB) receptor EC(50) 25 micro M, Hill coefficient 0.9) and markedly altered receptor desensitization. Kinetic modeling suggested that homomeric receptors, but not heteromeric receptors, desensitize via an agonist-induced open-channel block. Furthermore, heteromeric 5-HT(3AB) receptor assemblies recovered much faster from desensitization than homomeric 5-HT(3A) receptor assemblies. Unexpectedly, the specific 5-HT(3) receptor agonist mCPBG induced an open-channel block at both homomeric and heteromeric receptors. Because receptor desensitization and resensitization massively affect amplitude, duration, and frequency of synaptic signaling, these findings are evidence in favor of a pivotal role of subunit composition of 5-HT(3) receptors in serotonergic transmission.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serotonin
/
Receptors, Serotonin
/
Kidney
/
Models, Biological
Type of study:
Evaluation_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Biophys J
Year:
2003
Document type:
Article
Affiliation country:
Germany