Li and Steinbach apply nonstationary noise analysis to the whole-cell current responses of low sensitivity alpha4beta2 nAChR stably-expressed in HEK cells. These receptors represent one of the most important nAChR subtypes in brain, and also one of the most difficult to study in native tissues. They found the activating properties of the full agonists ACh and nicotine to be similar with regard to P(open) and single channel conductance, whereas the weak alpha4beta2 partial agonist cytisine caused channels to open with low probability but increased single channel conductance. When optimally stimulated by either of the full agonists, approximately 80% of the available receptors opened at the peak of the response. However, comparisons of whole-cell current to estimates of total cell surface receptors, indicated that only about 7% of the total receptor population can be activated. These observations provide important and intriguing new pieces of the brain nicotine receptor puzzle.