Electrophysiological Techniques For Clinical Diagnosis

Electrophysiological techniques

Electrophysiology deals with the study of the flow of ions in biological tissues and the electrical recording techniques which enable visualizing and measuring this flow. Voltage changes can be measured from single ion channel proteins to whole organs and can be used for large scale recordings as well of the nervous system – electroencephalogy. There are various techniques both for intracellular and extracellular recordings which we will look at separately below:

Intracellular recording measures membrane potential in the resting membrane of a cell.

• Voltage clamp: allows the membrane potential to be controlled.
• Current clamp: this technique allow the recording of the membrane potential by injecting current into a cell; unlike the voltage clamp, the voltage may vary as it is not controlled.
• Patch – clamp: a microelectrode will apply suction close to a cell to draw a section of the cell membrane through the microelectrode tip.
• Sharp electrode technique: allows recording the potential inside a cell membrane without affecting the ionic constitution of the intracellular fluid.

Extracellular recording

• Single-unit recording: an electrode can be introduced in the brain of an animal which is alive to record electrical activity in the adjacent neurons.
• Multi-unit recording: it is similar to the technique described above only it allows the recording of several neurons through a larger electrode tip.
• Field potentials: can be generated by the activation of multiple neurons by synaptic transmission.
• Amperometry: measures changing in voltage through a carbon electrode which records chemical composition of the oxidized components of a biological solution.

Other less frequently used methods are solid-supported membrane (SSM) and bioelectric recognition assay (BERA). Computational electrophysiology is not an experimental measurement but methods have been developed for the in silico study of the conductive properties of proteins.

Studying neurotransmitters

Neurotransmitters are nervous system molecules which allow communication between cells which generate a physiological response which can be recorded through electrophysiology as neurotransmitters act by opening membrane ion channels. At synapses, presynaptic action potentials open voltage gated calcium channels, which allows calcium to enter and trigger the release of a neurotransmitter. Neurotransmitters are one of the key players in a neuron and transmit messages called action potentials, which is an electrochemical impulse travelling down the axon. Cellular membranes are charged electrically due to ions in the extracellular and intracellular space.

Of all the techniques described above, the current clamp is the best technique to study how neurons respond to neurotransmitters because it can study how a cell responds when electric current enters a cell. Secondary, the voltage clamp can also be used to measure the signal transmitted by neurotransmitters as this technique would allow measuring how much ionic current crosses a cell’s membrane at a set level of voltage. Some of the voltage gated ion channels only open within a certain range of voltage.

Unsuitable methods

The sharp electrode technique would not be very suitable to measure the action of a novel neurotransmitter because penetrating the cell interior with an electrode in order to measure the intracellular potential may damage the membrane and affect the cytoplastic miliu which would give rise to highly distorted results.

The extra cellular techniques would also not be highly suitable due to the constrictions on the recording time which is often under 3 hours. Even though multiple sessions can be recorded, this is a limitation.

Model for other studies using electrophysiological techniques

In the case that a new neurotransmitter were discovered and studied, one would have to replicate previous studies done on famous neurotransmitters such as dopamine or serotonin.

There were some successful attempts using labeled 2-deoxyglucose in conjunction with PET and, later one through functional magnetic resonance imaging. The current clamp has been used to record dopamine signals in a number of studies therefore may be suitable for other newly developed neurotransmitters.