CHRONIC, INTERMITTENT LOADING ALTERS MECHANOSENSITIVE CHANNEL CHARACTERISTICS IN OSTEOBLAST-LIKE CELLS

The effects of chronic, intermittent strain on the mechanosensitive ca tion (SA-cat) channels in UMR-106.01 osteoblast-like osteosarcoma cell s were studied using patch-clamp techniques. Chronically strained cell s demonstrated significantly larger increases in whole cell conductanc e when subjected to additional mechanical strain than nonstrained cont rols (69.0 +/- 15.1 vs. 14.1 +/- 3.1%; P < 0.001). This increase could be blocked by the SA-cat channel inhibitor, gadolinium, and correspon ded to a three- to fivefold increase in SA-cat channel activity. Chron ic strain increased the number of open channels in response to stretch and induced spontaneous SA-cat channel activity in 33% of the patches of strained cells. Graded increases in negative patch pressure demons trated that SA-cat channels in chronically strained cells were activat ed at significantly lower levels of mechanical perturbation than nonst rained controls. These data suggest that chronic, cyclic strain reduce s the activation threshold of the SA-cat channel and further strengthe n our hypothesis that this channel may act as a mechanotransducer for the activation of bone remodeling by physical strain.