Involvement of Na(+)-K(+)-2Cl(-) cotransporters in hypertonicity-induced rise in intracellular calcium concentration.

A hypertonic saline containing propylene glycol facilitates calcium (Ca(2+)) influx through voltage-dependent Ca(2+) channels. The present study performed experiments to elucidate the mechanism by which Na(+)-K(+)-2Cl(-) cotransporters participate in the rise in the intracellular calcium concentration ([Ca(2+)]i) under the hypertonic condition. Both furosemide and ethacryonic acid significantly decreased the [Ca(2+)]i raised by hypertonicity. Similarly, Na(+)-, K(+)-, or Cl(-)-free saline also reduced it. Both norepinephrine and dopamine significantly enhanced the rise in [Ca(2+)]i. In conclusion, the findings obtained indicate that the Na+-K+-2Cl- cotransporters evoke cell depolarization and that this depolarization raises the [Ca(2+)]i by activating voltage-dependent Ca(2+) channels.