CONDUCTANCE AND PERMEATION OF MONOVALENT CATIONS THROUGH DEPLETION-ACTIVATED CA2-CRAC) IN JURKAT T-CELLS( CHANNELS (I)

We studied monovalent permeability of Ca2+ release-activated Ca2+ chan nels (I-CRAC) in Jurkat T lymphocytes following depletion of calcium s tores. When external free Ca2+ ([Ca2+](o)) was reduced to micromolar l evels in the absence of Mg2+, the inward current transiently decreased and then increased approximately sixfold, accompanied by visibly enha nced current noise. The monovalent currents showed a characteristicall y slow deactivation (tau = 3.8 and 21.6 s). The extent of Na+ current deactivation correlated with the instantaneous Ca2+ current upon readd ition of [Ca2+](o). No conductance increase was seen when [Ca2+](o) wa s 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 -8 0 mV was Na+ > Li+ = K+ > Rb+ much greater than Cs+. Unitary inward co nductance of the Na+ current was 2.6 pS, estimated from the ratios Del ta sigma(2)/Delta/mean at different voltages. External Ca2+ blocked th e Na+ current reversibly with an IC50 value of 4 mu M. Na+ currents we re 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 exter nal divalent ions. In contrast to voltage-activated Ca2+ channels, the monovalent conductance is highly selective for Na+ over Cs+. Na+ curr ents through I-CRAC channels provide a means to study channel characte ristics in an amplified current model.