SUMMARY1. Previous work has.shown that the sodium efflux from the axons of Loligo forbesi increa 2. The increase in efflux in lithium was unaffected by ouabain but was abolished by removal of external calcium; in these respects it differed from the potassium-dependent sodium efflux which was abolished by ouabain but not reduced by removal of external calcium.3. Strontium but not magnesium could replace calcium in activating the ouabain-insensitive sodium efflux; lanthanum had an inhibitory effect.4. Replacing all the holine chloride or dextrose gave a rise in Na efflux which was abolishey ouabain but not by removal of external calcium.5. The rise in Na efflux resulting from partial replacement of NaCl by dextrose or choline chloride consisted of two components one of which was ouabain-insensitive and calcium-dependent and the other was inhibited by ouabain but calcium-insensitive.6. The ouabain-insensitive component of the Na efflux was activated by low concentrations of Na, Li or K but inhibited by high concentrations of Na and to a lesser extent Li. The inhibiting effect of high Na was of the kind expected if these ions displace calcium from an external site.7. The ouabain-insensitive component of the Na efflux was abolished by cyanide, had a Qlo of 2-7; and was roughly proportional to [Na]?. It was much more variable in magnitude than the ouabain-sensitive, potassiumdependent component of the sodium efflux. 8. The calcium influx increased five to fortyfold when external NaCl

somes: veratridine (7.5 x 106 to 7-5 x 10-5 M) and scorpion (Leirus quinquestriatus) venom (6-7 x 10-7 to 6-7 x 10-6 g/ml.

Page C165: M. P. Blaustein. “Sodium ions, calcium ions, blood pressure regulation, and hypertension: a reassessment and a hypothesis.” Page C169: left column, paragraph 2, line 9 should read (with Na rate coefficient k-1). Page C170: left column, top paragraph, lines 21–22 should read total cell Ca will increase by about 4–40 micromoles per liter fiber water. Left column, top paragraph, lines 23–24 should read 1,000–1,500 micromoles per liter fiber water.

SUMMARY1. Some physiological properties of tissue fractions from rat brain homogenates have been examined. Of the three fractions studied (presynaptic nerve terminals, mitochondria and fragmented membranes), only the nerve terminals (synaptosomes) have the ability to accumulate 42K from physiological salt solutions.2. The ability to accumulate and retain K is lost if synaptosomes are exposed to very hypotonic solutions. The K uptake and total K content is reduced by ouabain and by inhibitors of glycolysis and oxidative phosphorylation.3. These results suggest that synaptosomes in physiological saline accumulate K against a concentration gradient, and may have K diffusion potentials across their surface membranes. The voltage-sensitive fluorescent probe, 3,3'-dipentyl 2,2'-oxacarbocyanine (CC5.), was used to test this possibility.4. In the squid axon, the fluorescent emission of CC5 is directly proportional to membrane potential; depolarization causes an increase in fluorescence.5. The fluorescence of synaptosomes ('synaptosome fluorescence') treated with CC5 is increased when [K] 11. The veratridine-induced increase in synaptosome fluorescence was prevented by 3 x 10-7 M tetrodotoxin, which also blocks the depolarizing effect of veratridine in intact neurones.12. The main conclusion is that synaptosomes may retain resting membrane potentials and the ability to increase Na permeability.

Calcium-45 efflux was measured in squid axons whose internal solute concentration was controlled by internal dialysis. Most of the Ca efflux requires either external Na (Na-Ca exchange) or external Ca plus in alkali metal ion (Ca-Ca exchange; cf. Blaustein & Russell, 1975). Both Na-Ca and Ca-Ca exchange are apparently mediated by a single mechanism because both are inhibited by Sr and Mn, and because addition of Na to an external medium optimal for Ca-Ca exchange inhibits Ca efflux. The transport involves simultaneous (as opposed to sequential) ion counterflow because the fractional saturation by internal Ca (Cai) does not affect the external Na (Nao) activation kinetics; also, Nao promotes Ca efflux whether or not an alkali metal ion is present inside, whereas Ca-Ca exchange requires alkali metal ions both internally and externally (i.e., internal and external sites must be appropriately loaded simultaneously). ATP increases the affinity of the transport mechanism for both Cai and Nao, but it does not affect the maximal transport rate at saturating [Ca2+]i and [Na+]o; this suggest that ATP may be acting as a catalyst of modulator, and not as an energy source. Hill plots of the Nao activation data yield slopes congruent to 3 for both ATP-depleted and ATP-fueled axons, compatible with a 3 Na+-for-1 Ca2+ exchange. With this stoichiometry, the Na electrochemical gradient alone could provide sufficient energy to maintain ionized [Ca2+]i in the physiological range (about 10(-7) M).