A Molecular Structural Basis for the Excitation Properties of Axons

Goldman, David E.

doi:10.1016/s0006-3495(64)86776-x

Cited by 173 publications

(50 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is reasonable to assume that this gate is open at the outer surface of the nerve membrane in view of the insolubility of T T X in lipids. The gate is probably controlled by membrane potential and calcium (Goldman, 1964). High external calcium concentration has been shown to interact with the blocking action of T T X (Takata et al, 1966), and this is consistent with the above mentioned notion.…”

Section: The M a X I M U M Values F O R T H E Early T R A N S I E N Tsupporting

confidence: 81%

Comparison of Tetrodotoxin and Procaine in Internally Perfused Squid Giant Axons

Narahashi

Anderson

Moore

1967

The Journal of General Physiology

105

View full text Add to dashboard Cite

Squid giant axons were internally perfused with tetrodotoxin and procaine, and excitability and electrical properties were studied by means of current-clamp and sucrose-gap voltage-clamp methods. Internally perfused tetrodotoxin was virtually without effect on the resting potential, the action potential, the early transient membrane ionic current, and the late steady-state membrane ionic current even at very high concentrations (1,000-10,000 nM) for a long period of time (up to 36 min). Externally applied tetrodotoxin at a concentration of 100 r~ blocked the action potential and the early transient current in 9-3 min. Internally perfused procaine at concentrations of 1-10 mM reversibly depressed or blocked the action potential with an accompanying hyperpolarization of 2-4 mv, and inhibited both the early transient and late steady-state currents to the same extent. The time to peak early transient current was increased. The present results and the insolubility of tetrodotoxin in lipids have led to the conclusion that the gate controlling the flow of sodium ions through channels is located on the outer surface of the nerve membrane.Selective blockage of the early transient ionic conductance increase by tetrodotoxin (TTX), the active component of the toxins from the puffer fish and California newt, has been well established in giant axons of lobster (Narahashi, Moore, and Scott, 1964; Takata, Moore, Kao, and Fuhrman, 1966) and squid (Moore, Blaustein, Anderson, and Narahashi, 1967; Nakamura, Nakajima, and Grundfest, 1965 a) and in electroplaques of eel (Nakamura, Nakajima, and Grundfest, 1965 b), since this mechanism was first suggested from studies on frog muscle fibers (Narahashi, Deguchi, Urakawa, and Ohkubo, 1960; Nakajima, Iwasaki, and Obata, 1962). Because of its very strong affinity for the early transient channel, T T X has now become a powerful tool for characterizing the conductance changes responsible for excitation.In contrast, procaine blocks both the early transient and the late steadystate conductance changes (Taylor, 1959; Shanes, Freygang, Grundfest, and ~4x3 The Journal of General Physiology Amatniek , 1959; Blaustein and Goldman, 1966). Procaine differs from T T X not only in this nonselective blockage but also in its much higher threshold concentration and its effect on the kinetics of the early transient conductance increase (Takata et al., 1966). In the meantime the internal perfusion technique has been developed for squid axons (Baker, Hodgkin, and Shaw, 1961; Oikawa, Spyropoulos, Tasaki, and Teorell, 1961), giving us a straightforward approach for study of symmetry or asymmetry of the nerve membrane with respect to the action of various agents (Narahashi, 1963(Narahashi, , 1965 Baker, Hodgkin, and Shaw, 1962; Tasaki, Watanabe, and Takenaka, 1962; Tasaki and Takenaka, 1964;Rojas, 1965). Since T T X is insoluble in most organic solvents (Mosher, Fuhrman, Buchwald, and Fischer, 1964) and hence most probably so in lipids, it would be expected to block the early transient con...

show abstract

Section: The M a X I M U M Values F O R T H E Early T R A N S I E N Tsupporting

confidence: 81%

Comparison of Tetrodotoxin and Procaine in Internally Perfused Squid Giant Axons

Narahashi

Anderson

Moore

1967

The Journal of General Physiology

105

View full text Add to dashboard Cite

show abstract

“…2), it appeared to be the trivalent cation most likely not to bind at all to the axonal membrane.) The calculation of the approximate density of surface charges on the membrane is achieved through use of the (0) (Goldman, 1964;D'Arrigo, 1972) that the axonal membrane in the region surrounding a sodium 'gate' is essentially represented by a phospholipid bilayer. At the same time, the agreement provides indirect support for those theories (Goldman, 1964;Wang, 1970;Wei, 1971;D'Arrigo, 1972) which ascribe the voltage-dependent, sodium 'gating' function to the polar complexes of membrane phospholipids, although most of these proposals have been shown to contain serious inadequacies (D'Arrigo, 1972).…”

Section: Discussionmentioning

confidence: 99%

“…The calculation of the approximate density of surface charges on the membrane is achieved through use of the (0) (Goldman, 1964;D'Arrigo, 1972) that the axonal membrane in the region surrounding a sodium 'gate' is essentially represented by a phospholipid bilayer. At the same time, the agreement provides indirect support for those theories (Goldman, 1964;Wang, 1970;Wei, 1971;D'Arrigo, 1972) which ascribe the voltage-dependent, sodium 'gating' function to the polar complexes of membrane phospholipids, although most of these proposals have been shown to contain serious inadequacies (D'Arrigo, 1972). In consideration of the number of electrophysiological and pharmacological properties common to most axons (see Hille, 1970;D'Arrigo, 1972), it seems improbable that the axonal membrane is structured very differently in different types of axons.…”

Section: Discussionmentioning

confidence: 99%

Possible screening of surface charges on crayfish axons by polyvalent metal ions

D'Arrigo¹

1973

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. The effect of different polyvalent metal ions in the external solution upon the threshold membrane potential for spike initiation in crayfish axons has been studied by means of intracellular micro-electrodes. The metal ions tested included six divalent cations (Ca2+, Mg2+, Sr2+, Ba2+, Co2+, and Ni2+) and three trivalent cations (La +, Y3+ and Eu3+).2. Identical extracellular concentrations of different cations with the same valence had essentially the same effect on threshold membrane potential. However, a very low concentration of trivalent cations (about 225 /SM) was found to be equivalent to a much higher divalent cation concentration (13.5 mM) as measured by their effects on threshold potential.3. Upon a tenfold increase in concentration, the threshold potential for spike initiation was shifted in a positive direction by 30-6 mV with divalent cations and by 208 mV with trivalent cations.4. It is shown that a hypothesis involving screening of negative charges at the axonal membrane surface, based on Gouy-Chapman theory, predicts these various experimental results rather closely.5. It is concluded that a high negative charge density, sufficient to render a screening mechanism possible, exists at the surface of crayfish axons in the region of the sodium 'gates'. 6. The density of surface charges is calculated to be approximately le-/43 A2. This calculation is discussed in connexion with the possible molecular identity of the sodium 'gates' in crayfish axons and other excitable systems.

show abstract

“…Tasaki (1968) suggested that it would seem reasonable to regard any pores that might exist in the membrane as dynamic, time dependent structures, rather than as rigid, static holes. Goldman (1964) also felt that it was highly unlikely that individual channels for the ions are established by any rigid structure. He felt that the phosphate groups of the membrane act as exchange sites through which the ions pass as they rush through the membrane.…”

Section: Resultsmentioning

confidence: 99%

“…He suggested that initiation of an active response occurred when the ratio of divalent ions to univalent ions in the cell membrane was reduced to a critical value. Goldman (1964) theorized that the calcium ions could corrbine with the exchange sites and form an area having the characteristic of low conductance for specific ions. He felt that changes in the electric field and thermal agitation could modify the binding properties of the phosphate groups at the ex change sites causing a change in the characteristics of the membrane.…”

Section: Resultsmentioning

confidence: 99%

The effect of divalent cations upon the membrane potential of the crayfish giant axon

Hallgren

View full text Add to dashboard Cite

A Molecular Structural Basis for the Excitation Properties of Axons

Cited by 173 publications

References 9 publications

Comparison of Tetrodotoxin and Procaine in Internally Perfused Squid Giant Axons

Comparison of Tetrodotoxin and Procaine in Internally Perfused Squid Giant Axons

Possible screening of surface charges on crayfish axons by polyvalent metal ions

The effect of divalent cations upon the membrane potential of the crayfish giant axon

Contact Info

Product

Resources

About