Co-ordinated expression of 5-HT2C receptors with the NCX1 Na+/Ca2+ exchanger in histaminergic neurones.
The different roles of Na+/Ca2+ (NCX) exchangers and Na+/Ca2+/K+ (NCKX) exchangers in regulation of the ionic homeostasis in neurones are poorly understood. We have previously shown that serotonin excites histaminergic tuberomamillary (TM) neurones by activation of 5-HT2C-receptors and Na+/Ca2+ exchange. With the help of single-cell RT-PCR (sc-RT-PCR) we have now determined the coexpression pattern of different subtypes of NCX and NCKX with serotonin receptors. The majority of TM neurones express NCX1, NCX2 and NCKX3. Serotonin 2C receptor-mRNA was detected in 70% while 5-HT2A mRNA was found in only 10% of TM neurones. In all neurones expressing the 5-HT2C receptor NCX1-mRNA was present. Double immunostaining revealed the presence of the NCX1 protein in histidine decarboxylase-positive neurones. In the majority of TM neurones one or two out of five isoforms, NCX1.4, NCX1.5, NCX1.7, NCX1.14, NCX1.15, were detected by cDNA sequencing and/or by restriction analysis. The alternative splicing region is important for the Ca2+ sensitivity and presumably for the modulation of NCX1 function by second messengers. We conclude that several exchanger-subtypes can be coexpressed in single neurones and that TM cells are heterogeneous with respect to their calcium homeostasis regulation.
Sergeeva
O A
OA
Department of Neurophysiology, Heinrich-Heine-Universität, Düsseldorf, Germany. Olga.Sergeeva@uni-duesseldorf.de
Amberger
B T
BT
Eriksson
K S
KS
Scherer
A
A
Haas
H L
HL
D017398:Alternative Splicing; D000818:Animals; D015870:Gene Expression; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000096:biosynthesis; D007026:Hypothalamic Area, Lateral / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D005810:Multigene Family; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; C511590:Slc24a3 protein, rat; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; C074530:potassium-dependent sodium-calcium exchanger; D006632:Histamine; D006640:Histidine Decarboxylase