Chronic, intermittent loading alters mechanosensitive channel characteristics in osteoblast-like cells

Abstract

The effects of chronic, intermittent strain on the mechanosensitive cation (SA-cat) channels in UMR-106.01 osteoblast-like osteosarcoma cells were studied using patch-clamp techniques. Chronically strained cells demonstrated significantly larger increases in whole cell conductance when subjected to additional mechanical strain than nonstrained controls (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 corresponded to a three- to fivefold increase in SA-cat channel activity. Chronic 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 demonstrated that SA-cat channels in chronically strained cells were activated at significantly lower levels of mechanical perturbation than nonstrained controls. These data suggest that chronic, cyclic strain reduces the activation threshold of the SA-cat channel and further strengthen our hypothesis that this channel may act as a mechanotransducer for the activation of bone remodeling by physical strain.