SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) application note: (0.8 MB)
Cells were engineered and kindly provided by SB Drug Discovery.
Nicotinic Acetylcholine Receptors (nAChR) are cationpermeable ion channels, which mediate fast synaptic transmission when activated by the endogenous neurotransmitter acetylcholine (ACh) and the exogenous natural alkaloid, nicotine. Neuronal nAChR form pentameric channels which are composed of two α (α2 to α10) and three β subunits (β2 to β4). Mutations of nAChR are associated with some forms of epilepsy and many other neurological disorders such as Alzheimer’s Disease, Parkinson’s, Tourette’s Syndrome, Schizophrenia and depression. The most abundantly expressed nAChR in the mammalian brain are the α7 homomeric and α4β2 heteromeric receptors. In contrast to the α7, a4β2 nAChR has a high affinity for nicotine. This property, the up-regulation during chronic exposure to nicotine, and the receptor expression location in addiction sensitive regions of the brain like the ventral tegmental area, strongly indicate that the a4β2 nAChR is a potential target for addiction to nicotine. Here we present data collected on the SyncroPatch 384PE showing activation and block of α4β2 nAChR currents expressed in HEK cells with rapid application of ligand (‘Ligand Puff’). ACh activates α4β2 nAChR in a concentration dependent manner with an EC50 value similar to those reported in the literature. Reproducible currents were achieved when cells were preincubated with
acetylcholinesterase (AChE). Finally, α4β2 nAChR were blocked by dihydro-b-erythroidine hydrobromide (DHßE), a well known competitive antagonist of the α4 subunit3 with an IC50 in good agreement with the literature.