Cation permeability change caused by l-glutamate in cultured rat hippocampal neurons

The ionic mechanism of the membrane permeability changes caused by l-glutamate in hippocampal neurons prepared from 17- to 19-day-old fetal rat in dispersed cell cultures was studied with the whole-cell variation of the patch electrode voltage-clamp technique. The cultured hippocampal neurons became sensitive to glutamate 7 days after plating, and thereafter the sensitivity gradually increased. The conductance increase caused by glutamate was voltage-sensitive, decreasing with membrane hyperpolarization at potentials more negative than -40 mV. The relative permeability of glutamate-activated channels to alkali metal and alkaline earth cations was estimated by reversal potential measurements. The alkali metal cations, Li+, Na+, K+, Rb+ and Cs+ were permeant to the glutamate channels, and the selectively among them was weak. The alkaline earth cations, Ca²⁺, Sr²⁺ and Ba²⁺ were more permeant than the alkali metals. The permeability ratios of these divalent cations relative to Na+ were 2.4 (Ca²⁺), 2.4 (Sr²⁺) and 2.8 (Ba²⁺), respectively. Mg²⁺ was much less permeant and the permeability ratio (P_Mg/P_Na) was only 0.1. Anion conductance made no contribution to the glutamate-induced current. Functional implications of the glutamate-induced increase in Ca²⁺-influx were discussed.