Figure 13. The energy landscape of AChR desensitization.

The relative free energy along the desensitization reaction coordinate was calculated from the cell-attached patch (1 mm ACh) rate constants using a five-state linear kinetic model (Table 2). The height of the barriers (dotted lines) is arbitrary. The first step is uphill (∼2 k_BT), followed by plateau consisting of three small downhill steps (∼1.5 k_BT each) and, finally, a steep downhill step (∼5 k_BT). As desensitization proceeded, the barrier heights increased.