Potential transmembrane

In Section 19.2 we already mentioned the existence of an electric potential difference between the two sides, 1 and 2, of the membrane the transmembrane potential = % - /i. For biological membranes, the cytoplasmic side is usually denoted as side 2 and the extracellular side as side 1. As a rule Axi/ attains negative values of a few tens of mV. 

The transmembrane potential results from different ion permeabilities for different ions and from different ion concentrations at the two sides of the membrane. 

Consider the simple case of a membrane-enclosed solution of a (low molecular weight) electrolyte immersed in its solvent. If the manbrane is permeable 

Membrane potentials as expressed by Equation 19.13 that result solely from semipermeability of the membrane are called Nernst potentials. 

In Section 9.5, we discussed the Donnan effect, that is, the expulsion of electrolyte from an electrical double layer around a charged surface or a polyelectrolyte. It has been shown that the Donnan effect leads to an unequal distribution of ions between the double layer and the bulk solution and, hence, to an electric potential difference, the Donnan potential. Thus, the Donnan potential is a special case of the Nemst potential. 

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Retention, too, is highly tissue-specific. Sometimes, the extraction mechanism is also the retention mechanism, as for Tc-sestamibi, which is retained in mitochondria as long as transmembrane potentials remain intact. Others are separate. F-2-Fluorodeoxyglucose enters the cell by the same pathway as glucose, but is trapped because it is not a substrate for hexokinase, preventing further intracellular metabohsm. 

Fig. 1. (a) Myocardial ceU transmembrane potentials, where the numbers and letters refer respectively to the phases and waves described in the text. ECG is... 

Conductivity. Conductivity is an electrical property of excitable tissue which ensures that if one area of a membrane is excited to full activity, that area excites adjacent areas. Conduction of an impulse varies direcdy with the rate of development of phase 0 and the ampHtude of the action potential. Phase 0 is faster, and ampHtude of the action potential is greater, the more negative the transmembrane potential at the time of initiation of the impulse. Conduction velocity is faster when phase 0 is fast. 

Fig. 7. A. Kinetic scheme for two site single filing channel. Ten rate constants are required. In the absence of a transmembrane potential, however, the two-fold symmetry of the channel reduces this to five rate constants. Then Eyring rate theory is used to introduce the voltage dependence as shown in Eq. 6.

Utilizing the above five experimentally derived rate constants and Eyring rate theory, the ten rate constants of Eq. 6 are all obtained. With the rate constants known, the probability of each occupancy state, /(ox) for example, can be calculated and finally the single channel current can be calculated as a function of molal activity of sodium ion. This is done for a 100 mV transmembrane potential in Fig. 9. It should be emphasized that Fig. 9 represents a calculation of single channel currents... 

The transmembrane potential derived from a concentration gradient is calculable by means of the Nemst equation. If K+ were the only permeable ion then the membrane potential would be given by Eq. 1. With an ion activity (concentration) gradient for K+ of 10 1 from one side to the other of the membrane at 20 °C, the membrane potential that develops on addition of Valinomycin approaches a limiting value of 58 mV87). This is what is calculated from Eq. 1 and indicates that cation over anion selectivity is essentially total. As the conformation of Valinomycin in nonpolar solvents in the absence of cation is similar to that of the cation complex 105), it is quite understandable that anions have no location for interaction. One could with the Valinomycin structure construct a conformation in which a polar core were formed with six peptide N—H moieties directed inward in place of the C—O moieties but... 

Fig. 5. Tentative mixed potential model for the sodium-potassium pump in biological membranes the vertical lines symbolyze the surface of the ATP-ase and at the same time the ordinate of the virtual current-voltage curves on either side resulting in different Evans-diagrams. The scale of the absolute potential difference between the ATP-ase and the solution phase is indicated in the upper left comer of the figure. On each side of the enzyme a mixed potential (= circle) between Na+, K+ and also other ions (i.e. Ca2+ ) is established, resulting in a transmembrane potential of around — 60 mV. This number is not essential it is also possible that this value is established by a passive diffusion of mainly K+-ions out of the cell at a different location. This would mean that the electric field across the cell-membranes is not uniformly distributed.

Mansueto et al. suggested that the susceptibility of embryos to toxicants could be first related to their interaction with egg membrane where they could provoke changes of permeability, of transmembrane potential, and of receptors distribution which could in turn drastically interfere with normal cell physiology. Cima et al. observed that TBT alters, immediately after the entry of... 

Nucleotide pools and transmembrane potential in bacteria after exposure to penta-chlorophenol were investigated using P NMR. Differences were used to differentiate Escherichia coli, which does not degrade this substrate and a Flavobacterium sp., which is able to do so (Steiert et al. 1988). 

When the original compositions of the outer phases are different, the permselective membrane will prevent the complete leveling of these compositions. Some equilibrium component distribution between phases (a) and (p) will be established, and between points A and B a potential difference called the membrane potential (or transmembrane potential) (p will develop. This potential difference is determined by... 

In medical practice, methods and instruments relying on electrochemical principles are widely nsed in diagnosing various diseases. The most important ones are electrocardiography, where the transmembrane potential of the muscle cells during contraction of the heart mnscle is measured, and electroencephalography, where impulses from nerve cells of the brain are measured. They also include the numerous instruments nsed to analyze biological fluids by electrochemical methods (see also Section 30.3). 

Inayat-Hussain SH, Annuar BO, Din LB, Ali AM, Ross D. Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells. Toxicol In Vitro 2003 17 433-439. 

The involvement of mitochondria in the pro-apoptotic effects of carotenoids has been clearly demonstrated by the fact that P-carotene induces the release of cytochrome c from mitochondria and alters the mitochondrial membrane potential (Aym) in different tumor cells (Palozza et al., 2003a). Moreover, the highly polar xanthophyll neoxanthin has been reported to induce apoptosis in colon cancer cells by a mechanism that involves its accumulation into the mitochondria and a consequent loss of mitochondrial transmembrane potential and releas of cytochrome c and apoptosis-inducing factor (Terasaki et al., 2007). 

Necrosis by LDH Mitochondrial transmembrane potential by DiOC6 and JC-1 fluorescence Apoptosis by cytochrome c release Annexin V binding DNA fragmentation by agarose gel electrophoresis... 

Because the fluorescence intensity changes observed in response to a change in transmembrane potential are much smaller when using fast dyes in comparison to... 

The transmembrane potential, A /, the surface potential, /s, and the dipole potential, /d, can be defined as follows ... 

Fig. 6 The electrical potential, ij/, profile across a lipid bilayer. The transmembrane potential, Aij/, is due to the difference in anion and cation concentrations between the two bulk aqueous phases. The surface potential, ij/s, arises from charged residues at the membrane-solution interface. The dipole potential, J/d, results from the alignment of dipolar residues of the lipids and associated water molecules within the membrane...

Slow dyes that respond via a redistribution across the entire membrane (sometimes called Nemstain dyes) do so because of a change in the transmembrane electrical potential. As such, they can only be used as probes of the transmembrane potential and not as probes of the surface potential or the dipole potential. Dyes whose electric field sensing mechanism involves a movement between the aqueous medium and its adjacent membrane interface on one side of the membrane can, in principle, respond to changes in both the transmembrane electrical potential and the surface potential. Fast dyes that remain totally in the membrane phase (e.g., styrylpyridinium, annellated hemicyanine, and 3-hydroxyflavone dyes) respond to their local electric field strength, whatever its origin. Therefore, these dyes can, in principle, be used as probes of the transmembrane electrical potential, the surface potential, or the dipole potential. 

Klymchenko AS, Stoeckel H, Takeda K et al (2006) Fluorescent probe based on intramolecular proton transfer for fast ratiometric measurement of cellular transmembrane potential. J Phys Chem B 110 13624-13632... 

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