Maxi K[sup +] channel mediates regulatory volume decrease response in a human bronchial epithelial cell line.

The cell regulatory volume decrease (RVD) response triggered by hypotonic solutions is mainly achieved by the coordinated activity of Cl[sup -] and K[sup +] channels. We now describe the molecular nature of the K[sup +] channels involved in the RVD response of the human bronchial epithelial (HBE) cell line 16HBE14o-. These cells, under isotonic conditions, present a K[sup +] current consistent with the activity of maxi K[sup +] channels, confirmed by RT-PCR and Western blot. Single-channel and whole cell maxi K[sup +] currents were readily and reversibly activated following the exposure of HBE cells to a 28% hypotonic solution. Both maxi K[sup +] current activation and RVD response showed calcium dependency, inhibition by TEA, Ba[sup 2+], iberiotoxin, and the cationic channel blocker Gd[sup 3+] but were insensitive to clofilium, clotrimazole, and apamin. The presence of the recently cloned swelling-activated, Gd[sup 3+]-sensitive cation channels (TRPV4, also known as OTRPC4, TRP12, or VR-OAC) was detected by RT-PCR in HBE cells. This channel, TRPV4, which senses changes in volume, might provide the pathway for Ca[sup 2+] influx under hypotonic solutions and, consequently, for the activation of maxi K[sup +] channels. [ABSTRACT FROM AUTHOR]