Membrane potential is the difference in voltage between the interior and exterior of a cell. The membrane potential allows a cell to function as a battery, providing power to operate a variety of molecular devices embedded in the membrane. In electrically excitable cells such as neurons, membrane potential is used for transmitting signals between different parts of a cell. Opening or closing of ion channels at one point in the membrane produces a local change in the membrane potential, which causes an electric current to flow rapidly to other points in the membrane. Ion channels have been identified as important drug discovery targets.
The plasma membrane of a cell typically has a transmembrane potential of approximately ?70 mV (negative inside) as a consequence of K+
concentration gradients that are maintained by active transport processes. Potentiometric probes offer an indirect convenient method of detecting the translocation of these ions although the fluorescent ion indicators can be used to directly measure changes in specific ion concentrations. Potentiometric optical probes enable researchers to perform membrane potential measurements in organelles and in cells that are too small for microelectrodes. Moreover, in conjunction with imaging techniques, these probes can be employed to map variations in membrane potential across excitable cells, in perfused organs and ultimately in the brain in vivo
with spatial resolution and sampling frequency that cannot be obtained using microelectrodes. Increases and decreases in membrane potential play a central role in many physiological processes, including nerve-impulse propagation, muscle contraction, cell signaling
and ion-channel gating.
Potentiometric probes are important tools for studying these processes, as well as for visualizing mitochondria
(which exhibit transmembrane potentials of approximately ?150 mV, negative inside matrix), for assessing cell viability and for high-throughput screening of new drug candidates. Potentiometric probes include the cationic or zwitterionic styryl dyes, the cationic carbocyanines and rhodamines, and the anionic oxonols. The class of dye determines factors such as accumulation in cells, response mechanism and toxicity. Selecting the best potentiometric probe for a particular application can be complicated by the substantial variations in their optical responses, phototoxicity and interactions with other molecules. There are two classes of membrane potential probes based on their response mechanisms: fast response and slow response membrane potential dyes.