Parallel patch clamp of alpha 7 nicotinic acetylcholine receptor channels

著者: Søren Friis, Morten Sunesen, Chris Mathes, Mark Bowlby, John Dunlop, Niels Willumsen

The human α7 nicotinic acetylcholine receptor (α7-nAChR) is a neuronal ligand-gated, fast desensitizing, non-selective cation channel. It is pentahomomeric, consisting of five 50 kD α7 subunits, each composed of 502 amino acids. The α7-nAChR is involved in memory and cognition, and it is widely distributed throughout the nervous system, especially in cholinergic neurons projecting to hippocampus and cortex. The α7-nAChR has also been found to be associated with pathophysiological states. Importantly, it is involved in widespread human neuro-degenerative and psychotic disorders, including Alzheimer’s disease and schizophrenia. Therefore the therapeutic potential of α7-nAChR is substantial, and electrophysiological and pharmacological characterization of the receptor has become an increasingly important issue. The fast kinetics (milliseconds) makes precise patch clamp measurements a challenging task. The present study addresses the possibility of efficient and precise characterization of α7-nAChR function and pharmacology by means of the QPatch automated patch clamp system. Compared to conventional whole-cell patch clamp the system enables a highly increased throughput by simultaneous and asynchronous operation of 16 parallel patch clamp experiments.