Activation of volume-regulated chloride currents by reduction of intracellular ionic strength in bovine endothelial cells

1. We have studied the effects of intracellular ionic strength (Gamma(i)) on the swelling-activated whole-cell Cl- current (I-Cl,I-swell) in cultured calf pulmonary artery endothelial cells (CPAE cells). 2. Reducing Gamma(1) from 155 to 95 mM at constant osmolarity and Cl- concentration activates an outwardly rectifying current that is mainly carried by Cl- ions and inactivates at positive potentials. The amplitude of the current is larger at more reduced levels of Gamma(i). 3. The permeability ratio for the anions I-, Br-, Cl- and gluconate (P-I: P-Br: P-Cl: P-gluc) was 1.35:1.03:1:0.17. 4. Blockers of the swelling-activated Cl- current in CPAE cells also inhibit the current which is activated by a reduction in Gamma(i) with an IC50 of 1.1 mu M for tamoxifen, 1.3 mu M for mibefradil, and 35 mu M for quinidine. 5. The protein tyrosine kinase inhibitors tyrphostin B46 (50 mu M) and genistein (100 mu M), which inhibit I-Cl,I-swell in CPAE cells, also inhibited the Gamma(1)-induced current by 92.9 +/- 2.4% (n = 3) and 41.2 +/- 5.0% (n = 4), respectively. 6. Hypertonic extracellular solutions rapidly and reversibly antagonized the Gamma(i)-activated current, whereas increasing Gamma(i) from 155 to 195 mM precluded activation of I-Cl,I-swell by hypotonic shock. 7. It is concluded that a reduction of Gamma(i) activates an anion current that is identical to that activated by cell swelling. Changes in intracellular ionic strength may shift the volume set point for activation of I-Cl,I-swell.