Volume regulation in the human airway epithelial cell line Calu-3

Cells regulate their volume in response to changes in the osmolarity of both their extracellular and their intracellular environments. We investigated the ability of the human airway epithelial cell line Calu-3 to respond to changes in extracellular osmolarity. Although switching Calu-3 cells from an isosmotic to a hyperosmotic environment resulted in cell shrinkage, there was no compensatory mechanism for the cells to return to their original volume. In contrast, switching to a hyposmotic environment resulted in an initial cell swelling response, followed by a regulatory volume decrease (RVD). Pharmacologic studies demonstrate that the voltage-activated K⁺ channels K _v4.1 and (or) K_v4.3 play a crucial role in mediating this RVD response, and we demonstrated expression of these channel types at the mRNA and protein levels. Furthermore, inhibition of the large- and intermediate-conductance Ca²⁺-activated K⁺ channels K _Ca1.1 (maxi-K) and K_Ca3.1 (hIK) also implicated these channels as playing a role in volume recovery in Calu-3 cells. This report describes the nature of volume regulation in the widely used model cell line Calu-3.