The Action of Certain Polyvalent Cations on the Voltage-Clamped Lobster Axon

Abstract

ABSTP.ACT Calcium appears to be an essential participant in axon excitation processes. Many other polyvalent metal ions have calcium-like actions on axons. We have used the voltage-clamped lobster giant axon to test the effect of several of these cations on the position of the peak inidal (sodium) and steadystate (potassium) conductance vs. voltage curves on the voltage axis as well as on the rate parameters for excitation processes. Among the alkaline earth metals, Mg +9 is a very poor substitute for Ca +s, while Ba +a behaves like "high calcium" when substituted for Ca +~ on a mole-for-mole basis. The transition metal ions, Ni +~, Co +s, and Cd +~ also act like high calcium when substituted mole-for-mole. Among the trivalent ions, La +8 is a very effective Ca +~ replacement. AI +a and Fe +8 are extremely active and seem to have some similar effects. A1 +8 is effective at concentrations as low as 10 -5 u. The data suggest that many of these ions may interact with the same cation-binding sites on the axon m e mbrane, and that the relative effects on the membrane conductance and rate parameters depend on the relative binding constants of the ions. The total amount of Na + transferred during a large depolarizing transient is nearly independent of the kind or amount of polyvalent ion applied. I N T R O D U C T I O NEvidence has long been available that calcium ions are intimately associated with the m e c h a n i s m of axon conduction (see Brink, 1954). Studies such as those of H 6 b e r (1920), and of G u t t m a n (1940) showed that the resting potential a n d excitability of axons can be effectively m a i n t a i n e d w h e n certain other divalent cations, particularly those of the alkaline earth series, are substituted for calcium. T h e effects of alkali metal ions on nerve excitability have been reviewed by Narahashi (1966). F r a n k e n h a e u s e r and H o d g k i n (I 957) studied the effects of calcium on the m e m b r a n e ionic conductances of voltagec l a m p e d squid axons. R e c e n t studies by D o d g e (1961) and by T a k a t a et al. (1966 b) demonstrate that nickel a n d l a n t h a n u m have certain effects on the electrical properties of voltage-clamped axons which are qualitatively similar 279

Pre- and post-synaptic effects of manipulating surface charge with divalent cations at the photoreceptor synapse

“…As discussed later, this block of I Ca was also accompanied by a block of post-synaptic responses. Mg 2+ has very weak surface charge effects relative to Ca 2+ so the left shift observed after lowering both Ca 2+ and Mg 2+ levels is almost completely due to the effects of lowering Ca 2+ on surface charge (Blaustein and Goldman, 1968;Hille et al, 1975;Hagiwara and Byerly, 1981). Partial recovery of I Ca was obtained after returning to control medium.…”

“…Zn 2+ exerts potent surface charge effects (Blaustein and Goldman, 1968;Hille et al, 1975) and is concentrated in photoreceptor terminals (Qian et al, 1997;Wu et al, 1993;Akagi et al, 2001). Fig.…”

“…Like Zn 2+ , Ni 2+ also exerts potent surface charge effects (Blaustein and Goldman, 1968;Hille et al, 1975). Accordingly, addition of Ni 2+ (5 μM; red trace) to the perfusion solution (Fig.…”

“…A quite different action was exerted on rod I Ca by Mg 2+ (N=9), a cation which has only a slight screening action on surface charges (Blaustein and Goldman, 1968;Hille et al, 1975;Hagiwara and Byerly, 1981). We had to increase Mg 2+ to 4 mM from its normal concentration of 0.5 mM to obtain a detectable effect on I Ca .…”

“…In another experimental approach, we bypassed the need for light stimulation entirely by testing the effects of low divalent cation solutions on post-synaptic currents (PSCs) evoked in OFF bipolar cells by depolarizing steps applied to simultaneously recorded presynaptic rods. Our study compared effects of Zn 2+ and Ni 2+ , which exert potent surface charge effects, with effects of Mg 2+ , which has weak surface charge effects (Blaustein and Goldman, 1968;Hille et al, 1975). Another reason for our interest in Zn 2+ is that this ion is concentrated in photoreceptor terminals and may be co-released with glutamate in synaptic vesicles (Akagi et al, 2001;Wu et al, 1993;Rosenstein and Chappell, 2003).…”