Ca Ions Block and Permeate Serotonin 5-HT3 Receptor Channels in Rat Hippocampal Interneurons

Van Hooft, Johannes A. and Wytse J. Wadman. Ca ions block and permeate serotonin 5-HT3 receptor channels in rat hippocampal interneurons. J Neurophysiol 89: 1864–1869, 2003. First published December 18, 2002; 10.1152/jn.00948.2002. The serotonin 5-HT3 receptor native to rat hippocampal CA1 stratum radiatum interneurons is blocked by Ca ions in a doseand voltage-dependent manner, which is reflected by a region of negative slope conductance in the I-V curve. The steep dependence on the extracellular Ca concentration suggests that the channel contains more than one binding site for Ca . A three barrier-two site model, based on Eyring rate theory, was used to describe the I-V curves. When extraand intracellular K and Cs were substituted with Na , the I-V curves were accurately fit by the model, unlike the I-V curves recorded under standard ionic conditions. This suggests that the K and Cs permeabilities are small compared with that of Na . The distribution of the energy barriers and binding sites for Ca and Na showed that the binding sites are located at approximately the 13 and the –4 position in the ion channel. The model predicts that at large hyperpolarized membrane potentials (more negative than 120 mV), the fractional Ca current amounts to approximately 1% of the total ion current. However, at physiologically relevant membrane potentials, the fractional Ca current is smaller ( 0.1%) and the relative Ca permeability (PCa/PNa) is estimated to be 0.10 at –60 mV.