Ca2+ Ions Block and Permeate Serotonin 5-HT3 Receptor Channels in Rat Hippocampal Interneurons

Abstract

The serotonin 5-HT₃receptor native to rat hippocampal CA1 stratum radiatum interneurons is blocked by Ca²⁺ 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 Ca²⁺concentration suggests that the channel contains more than one binding site for Ca²⁺. A three barrier-two site model, based on Eyring rate theory, was used to describe the I-Vcurves. 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 Ca²⁺ 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 Ca²⁺ current amounts to approximately 1% of the total ion current. However, at physiologically relevant membrane potentials, the fractional Ca²⁺ current is smaller (2+permeability ( P _Ca/ P _Na) is estimated to be 0.10 at –60 mV.