Squid axon

Traditionally concepts of ion selective permeation of biological membranes have centered on differences in the effective radii of hydrated nuclei. An example of that perspective derives from consideration of the resting membrane potential, E, which in the squid axon is approximated by the Nernst equation... 

Palytoxin (PTX) is one of the most potent marine toxins known and the lethal dose (LD q) of the toxin in mice is 0.5 Mg/kg when injected i.v. The molecular structure of the toxin has been determined fully (1,2). PTX causes contractions in smooth muscle (i) and has a positive inotropic action in cardiac muscle (4-6). PTX also induces membrane depolarization in intestinal smooth (i), skeletal (4), and heart muscles (5-7), myelinated fibers (8), spinal cord (9), and squid axons (10). PTX has been demonstrated to cause NE release from adrenergic neurons (11,12). Biochemical studies have indicated that PTX causes a release of K from erythrocytes, which is followed by hemolysis (13-15). The PTX-induced release of K from erythrocytes is depress by ouabain and that the binding of ouabain to the membrane fragments is inhibited by PTX (15). 

Suberitine, a small protein from the sponge Suberites domcuncula, has a variety of actions. It is not very toxic but causes hemolysis in human erythrocytes, flaccid paralysis in crabs and depolarization of squid axon and abdominal nerve of crayfish. A variety of extracts from Porifera have been shown to be toxic to fish and generally have cytotoxic and hemolytic actions (62,63). As discussed previously, a variety of sponges exude substances that are toxic to fish. 

Figure 2.2 Ionic conductances underlying the action potential recorded from a squid axon. gNa = Na conductance gK = K+ conductance. (Adapted from Hodgkin, AL and Huxley, AF (1952) J. Physiol. 117 500-544)...

Squid axons Lollgo pealii) H sealed-end all-glass microelectrode pH 7.3 144)... 

The transport of information from sensors to the central nervous system and of instructions from the central nervous system to the various organs occurs through electric impulses transported by nerve cells (see Fig. 6.17). These cells consist of a body with star-like projections and a long fibrous tail called an axon. While in some molluscs the whole membrane is in contact with the intercellular liquid, in other animals it is covered with a multiple myeline layer which is interrupted in definite segments (nodes of Ranvier). The Na+,K+-ATPase located in the membrane maintains marked ionic concentration differences in the nerve cell and in the intercellular liquid. For example, the squid axon contains 0.05 MNa+, 0.4 mK+, 0.04-0.1 m Cl-, 0.27 m isethionate anion and 0.075 m aspartic acid anion, while the intercellular liquid contains 0.46 m Na+, 0.01 m K+ and 0.054 m Cl-. 

Baker, P. F. (Ed.), The Squid Axon. Current Topics in Membranes and Transport, Vol. 22, Academic Press, Orlando, 1984. 

Conti, F., and E. Neher, Single channel recordings of K+ currents in squid axons, Nature, 285, 140 (1980). 

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

Armstrong, C.M. (1969) Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. The Journal of General Physiology, 54, 553-575. 

The clinical effects of chloroform toxicity on the central nervous system are well documented. However, the molecular mechanism of action is not well understood. It has been postulated that anesthetics induce their action at a cell-membrane level due to lipid solubility. The lipid-disordering effect of chloroform and other anesthetics on membrane lipids was increased by gangliosides (Harris and Groh 1985), which may explain why the outer leaflet of the lipid bilayer of neuronal membranes, which has a large ganglioside content, is unusually sensitive to anesthetic agents. Anesthetics may affect calcium-dependent potassium conductance in the central nervous system (Caldwell and Harris 1985). The blockage of potassium conductance by chloroform and other anesthetics resulted in depolarization of squid axon (Haydon et al. 1988). 

Haydon DA, Requena J, Simon AJB. 1988. The potassium conductance of the resting squid axon and its blockage by clinical concentrations of general anaesthetics. J Physiol 402 363-374. 

Nerve stimulation results in a net influx of sodium ions, and normal conditions are restored by the outward transport of sodium ions against an electrochemical gradient. While several earlier workers had identified ATPases in the sheath of giant squid axons, it was Skou who first connected the sodium, potassium ATPase [EC 3.6.1.37] with the ion flux of neurons. This discovery culminated... 

Further confirmation of the similarities in biological activities between aphantoxin and PSP was shown by Adelman et al. (1982) (30). They showed that crude preparations of aphantoxins blocked the Na channel of giant squid axon with equal potency as saxitoxin. 

Figure II. Membrane currents In voltage-clamped squid axons.

The a-dispersion is presently the least clarified. Intracellular structures, such as the tubular apparatus in muscle cells, which connect with the outer cell membranes, could be responsible in all such tissues which contain such cell structures. Relaxation of counterions about the charged cellular surface is another mechanism suggested by us. Last, but not least, relaxational behavior of membranes per se, such as reported recently for the giant squid axon membrane, can account for it (2). The relative contribution of the various mechanisms varies, no doubt, from one case to another and needs further elaboration. 

A model, based on a perturbation analysis of the highly successful empirical formulation of Hodgkin and Huxley (1), has been developed which makes predictions of the effect of oscillating fields on a particular nerve membrane system (2). In the present paper, a theoretical model will be presented along with some of the predicted effects of AC electric fields on the Hodgkin-Huxley (HH) model of squid axon membranes. 

Boron, W.F., Hogan, E., Russell, J.M. (1988). pH sensitive activation of intracellular pH regulation system in squid axons by ATPyS. Nature 332,262-265. 

Fig. 14.14. Unit for potential transient measurement during excitation of a squid axon by current pulses from electrodes 1 and 1 2 and 2 are micropipettes. (Reprinted from A. L. Hodgkin and A. F. Huxley, J. Physiol. 116 497, 1952. Reprinted from J. Koryta, Ions, Electrodes and Membranes, Fig. 93. Copyright J. Wiley Sons, Ltd. 1991. Reproduced with permission of J. Wiley Sons, Ltd.)...

In the Goldman equation use the diffusion coefficients in question 1 in place of permeation coefficients. The rate of permeation is -D(dc/dx). The dx is essentially the membrane thickness and its neglect will cancel out of the equation (cf. the Goldman equation), (c) Is this flux consistent with actual radiotracer measurements of the movement concerned (In the Hodgkin-Huxley and Katz work, arbitrary values were used for the P s to ensure that the equation replicated the experiment. This, of course, makes it difficult to check its validity. Assume the starting concentration of ions on either side of the membrane is that shown in the text. The average internal diameter of a squid axon is about 1 mm.)... 

The interaction of natural tetrazacyclopentazulenes with DNA, and their effects on the DNA and RNA polymerase reactions have been investigated (208). Paragracine (153) shows papaverine-like activity (203) and it selectively blocks sodium channels of squid axon membranes (209). 

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