Conductance and permeation of monovalent cations through depletion-activated Ca2+ channels (I-CRAC) in Jurkat T cells

We studied monovalent permeability of Ca2+ release-activated Ca2+ channels (I-CRAC) in Jurkat T lymphocytes following depletion of calcium stores. When external free Ca2+ ([Ca2+](o)) was reduced to micromolar levels in the absence of Mg2+, the inward current transiently decreased and then increased approximately sixfold, accompanied by visibly enhanced current noise. The monovalent currents showed a characteristically slow deactivation (tau = 3.8 and 21.6 s). The extent of Na+ current deactivation correlated with the instantaneous Ca2+ current upon readdition of [Ca2+](o). No conductance increase was seen when [Ca2+](o) was reduced before activation of I-CRAC. With Na+ outside and Cs+ inside, the current rectified inwardly without apparent reversal below 40 mV. The sequence of conductance determined from the inward current at -80 mV was Na+ > Li+ = K+ > Rb+ much greater than Cs+. Unitary inward conductance of the Na+ current was 2.6 pS, estimated from the ratios Delta sigma(2)/Delta/mean at different voltages. External Ca2+ blocked the Na+ current reversibly with an IC50 value of 4 mu M. Na+ currents were also blocked by 3 mM Mg2+ or 10 mu M La3+. We conclude that I-CRAC channels become permeable to monovalent cations al low levels of external divalent ions. In contrast to voltage-activated Ca2+ channels, the monovalent conductance is highly selective for Na+ over Cs+. Na+ currents through I-CRAC channels provide a means to study channel characteristics in an amplified current model.