Differentiation of NG108-15 cells alters channel conductance and desensitization kinetics of the 5-HT3 receptor.
1. NG108-15 cells undergo morphological differentiation in response to appropriate culture conditions. We have used patch clamp techniques to compare responses mediated by the 5-HT3 receptor in differentiated and undifferentiated NG108-15 cells. 2. In differentiated cells, desensitization of 5-hydroxytryptamine (5-HT) responses was much slower than in undifferentiated cells. Desensitization in differentiated cells was also highly variable, with half-times varying by greater than 40-fold. Rapidly desensitized responses in differentiated cells were qualitatively similar to the responses of undifferentiated cells. 3. In outside-out patches from undifferentiated cells, single channel currents could be seen after 5-HT application. These channels had a conductance of 12 pS. The 5-HT-activated channels in differentiated cells were too small to observe at the single-channel level. Noise analysis indicated that the channel conductance was approximately 4 pS. In differentiated cells, both rapidly and slowly desensitized responses were generated by channels with essentially the same conductance. 4. The 5-HT responses of differentiated cells were also distinguished from those of undifferentiated cells on the basis of the voltage dependence of desensitization and the curvature of the current-voltage curve. 5. NG108-15 cells can produce different receptor subtypes, which may be expressed in different tissues or at different stages of development. These variations in receptor behavior suggest that there are at least two distinct mechanisms for regulation of the 5-HT3 receptor.
Shao
X M
XM
Department of Physiology, University of Wisconsin, Madison 53706.
Yakel
J L
JL
Jackson
M B
MB
D002454:Cell Differentiation; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D011985:Receptors, Serotonin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D007473:Ion Channels; D011985:Receptors, Serotonin