Ca2+ ions block and permeate serotonin 5-HT3 receptor channels in rat hippocampal interneurons

The serotonin 5-HT(3) receptor native to rat hippocampal CA1 stratum radiatum interneurons is blocked by Ca(2+) ions in a dose- and 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(2+) concentration suggests that the channel contains more than one binding site for Ca(2+). A three barrier-two site model, based on Eyring rate theory, was used to describe the I-V curves. When extra- and 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(2+) 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(2+) current amounts to approximately 1% of the total ion current. However, at physiologically relevant membrane potentials, the fractional Ca(2+) current is smaller (<0.1%) and the relative Ca(2+) permeability (P(Ca)/P(Na)) is estimated to be 0.10 at -60 mV.