α7 at the single-channel level

Abstract

The α7 nicotinic receptor (nAChR) is expressed in brain and in non-neuronal cells. It is emerging as a drug target for cognitive deficits and inflammatory processes. We have focused on understanding α7 function at the single-channel level. We identified novel positive allosteric modulators (PAMs) and analyzed the activity of type I PAMs, which enhance macroscopic currents, and type II PAMs, which also decrease current decay rates. Regardless of their macroscopic behavior, all PAMs enhance open-channel lifetime and induce episodes of successive openings, indicating that both types affect α7 kinetics. We determined the temperature sensitivity and structural determinants for potentiation.