Neurons

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Importance of neuronal electrophysiology

Ion channels and transporters regulate neuronal excitability, which is crucial for normal brain function and changes in excitability underlie neurological disorders. Techniques such as patch clamp and solid-supported membrane-based (SSM) electrophysiology have revolutionized our understanding of these structures, enabling the development of targeted therapies. The patch clamp technique has historically been used to elucidate mechanisms involved in conditions including epilepsy, neurodegenerative diseases, and neuropathic pain, leading to therapies modulating specific ion channels as treatment targets. SSM electrophysiology allows the functional characterization of membrane transporters by recording transport currents via capacitive coupling, overcoming the limitations of conventional voltage clamp measurements. Together, these techniques have expanded our ability to study ion channels and transporters implicated in neurophysiology and various neurological disorders.

Recording neuronal activity using Automated Patch Clamp

Dynamic spectrum of neuronal functions

Neurons exhibit remarkable diversity in their morphology, neurotransmitter phenotype, and electrophysiological properties, which underlie the complexity of neural circuits and brain function. Recording from primary neurons and those derived from induced pluripotent stem cells (iPSCs) has been instrumental in understanding neuronal physiology, disease mechanisms, and drug screening. iPSC technology has accelerated neuronal research by providing an unlimited source of human neurons from various genetic backgrounds, enabling disease modeling and personalized medicine approaches. For instance, iPSC-derived neurons have facilitated investigations into pain research, neurodegenerative diseases including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, as well as neuropsychiatric disorders such as schizophrenia and autism.

Automated patch-clamp systems, such as the SyncroPatch 384 and the Patchliner have revolutionized the study of neuronal electrophysiology by enabling high-throughput and standardized recordings, overcoming the low-throughput limitations of manual patch-clamp. Co-cultures of neurons with other cell types, such as astrocytes or microglia, have provided insights into the complex interactions within the neural microenvironment and their impact on neuronal function and disease pathogenesis.

 

The figure shows NaV currents in RealDRGTM sensory neurons (Anatomic Incorporated, MN, USA), recorded with high success rates of more than 50%.  A IV plot at 28 DIV in the absence (blue) and the presence of TTX (red) recorded on the SyncroPatch 384. B Raw current traces from an example cell in the presence of TTX. C NaV current density decreases during maturation (total NaV current), and the Vhalf of activation of the TTXr current becomes more negative (D).

Neurotransmitter transporters are

important drug targets

Recordings of electrogenic transporters

Neurotransmitter transporters play a vital role in regulating neurotransmission by clearing released neurotransmitters from the synaptic cleft, thereby terminating their signaling effects. Dysregulation of these transporters is implicated in various neurological and psychiatric disorders, including depression, anxiety, addiction, and neurodegenerative diseases. Solid-supported membrane-based electrophysiology (SSME), the key technology behind the SURFE2R N1 and the SURFE2R 96SE enables direct electrical recordings of neurotransmitter transporter activity, providing invaluable insights into their functional mechanisms at the molecular level.

One example is the neurotransmitter γ-aminobutyric acid (GABA), which plays a pivotal role as an inhibitory neurotransmitter in the brain, and its regulation primarily relies on the activity of the GABA transporter hGAT1 within the central nervous system (CNS). hGAT1 is classified as a secondary-active transport protein, utilizing the sodium ion gradient to power the re-uptake of GABA from the synaptic cleft back into the presynaptic neuron. Given its association with numerous neurological disorders, dysregulation in GABA transport underscores the significance of hGAT1 as a therapeutic target. Using SSM-based electrophysiology, it is possible to record GABA-induced currents in plasma membrane vesicles that overexpressed hGAT1. The sensitivity of this method additionally allows for the investigation of cooperativity between the neurotransmitter and relevant ions as well as their stoichiometry.

Functional characterization of human GAT1 through SSM-based electrophysiology

Speakers:

Dr. Rocco Zerlotti

Organization: Nanion Technologies

Recording
neurons

Choose the best tools to analyse neuronal activity

 

Our portfolio of products offers versatile automated tools for in vitro dissection of neurophysiological and neuropathophysiological cellular phenotypes. The broad range and versatility of cell-based assays easily performed with these automated patch clamp and transporter research technologies, make them an excellent choice for integration into a core cell screening center/therapy/ biomanufacturing facility and traditional academic labs around the globe.

How can we help you?

Contact our specialist Dr. Alison Obergrussberger (Director of Scientific Sales and Customer Engagement). Alison is delighted to help you:

Ali.Obergrussberger@nanion.de

or call: +49 89 2190 95-078
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