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.