Neurons membrane potential

The styryl dye Di-4-ANEPPS (3.69) is a fast-responding membrane potential probe, particnlarly nsefnl for the studies of neuronal membrane potentials. 

Phenytoin s five-decades long existence as a clinical entity makes it one of the most studied anticonvulsants. In addition, it has antiarrhythmic activity (Chapter 10). At the physiological level the drug has been shown to influence ion conductance, neuronal membrane potentials, and the levels of most of the neurotransmitters discussed, including GABA. The extent to which any of these effects affect epilepsy is still not clear. Nevertheless, more recent research seems to point the finger toward a potentiation of GABA-mediated inhibition, at least as part of the answer. Valproic acid (Fig. 12-5) and... 

It is well known that the resting and dynamic electrical activity of the brain is a consequence of electrochemical potentials across membranes. Many other aspects of electrochemistry are also familiar in the neurosciences. Hence it may seem paradoxical to have suggested that the electro-analytical techniques are far afield of the mainstream of neurobiology. However, neuronal membrane potentials depend on ionic charge distributions and fluxes insofar as is known, electron current plays no role. Just the opposite is true for electroanalytical techniques—ionic conductance is of minimal importance but electron flow (current) is the essence of the measurement. The electrodes employed do not sense membrane potentials or respond to sodium or potassium fluxes rather, they pass small but finite currents because molecules close to their surface undergo oxidation or reduction. Such electrochemical measurements are called faradaic (because the amount of material converted at the electrode surface can be calculated from Faraday s law). 

Maintenance of electrical potential between the cell membrane exterior and interior is a necessity for the proper functioning of excitable neuronal and muscle cells. Chemical compounds can disturb ion fluxes that are essential for the maintenance of the membrane potentials. Fluxes of ions into the cells or out of the cells can be blocked by ion channel blockers (for example, some marine tox-... 

The M-channels (M for muscarine) are expressed in the peripheral sympathetic neurons and CNS. In the absence of acetylcholine, the M-channel opens at resting membrane potential and dampens neuronal responsiveness to synaptic inputs. Acetylcholine inhibits M-channel activity by activation of Ml receptor. 

An inhibitory input increases the influx of Cl to make the inside of the neuron more negative. This hyperpolarisation, the inhibitory postsynaptic potential (IPSP), takes the membrane potential further away from threshold and firing. It is the mirror-image of the EPSP and will reduce the chance of an EPSP reaching threshold voltage. 

Identity of action. The proposed NT must produce effects postsynaptically which are identical physiologically (appropriate membrane potential changes) and pharmacologically (sensitivity to antagonists) to that produced by neuronal stimulation and the relased endogenous NT. 

Figure 1.9 Comparison of the effects of an endogenously released and exogenously applied neurotransmitter on neuronal activity (identity of action). Recordings are made either of neuronal firing (extracellularly, A) or of membrane potential (intracellularly, B). The proposed transmitter is applied by iontophoresis, although in a brain slice preparation it can be added to the bathing medium. In this instance the applied neurotransmitter produces an inhibition, like that of nerve stimulation, as monitored by both recordings and both are affected similarly by the antagonist. The applied neurotransmitter thus behaves like and is probably identical to that released from the nerve...

Figure 11.5 Chloride distribution and the GABAa response. The change in membrane voltage (Fm) that results from an increase in chloride conductance following activation of GABAa receptors is determined by the resting membrane potential and the chloride equilibrium potential (Fci)- (a) Immature neurons accumulate CF via NKCC, while mature neurons possess a Cl -extruding transporter (KCC2). (b) In immature neurons GABAa receptor activation leads to CF exit and membrane depolarisation while in mature neurons the principal response is CF entry and h5q)erpolarisation. This is the classic inhibitory postsynaptic potential (IPSP)...

Nicholls, DG and Ward, MW (2000) Mitochondrial membrane potential and neuronal glutamate excitotoxicity mortality and millivolts. Trends Neurosci. 23 166-174. 

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