Competition between sodium and calcium ions in transmitter release at mammalian neuromuscular junction

Abstract

[Ca]. It was thought that this could be due to differences in chelation of Ca which were more apparent at low Ca concentrations.9. The similarities between the effects of Na, Ca and K on m.e.p.p. frequency and the effects of these ions on Ca-influx in heart muscle led to the suggestion that transmitter release is proportional to the concentration of a negatively charged complex of a carrier X with one calcium ion (CaX) at the internal surface of the membrane and that changes in membrane potential affect transmitter release by changing the distribution or location of CaX in the membrane.

The inhibitory effect of manganese on transmitter release at the neuromuscular junction of the toad

“…The relationship between m.e.p.p. frequency and [Ca] does not conform to a fourth power relationship (Del Castillo & Katz, 1954a;Hubbard, 1961 ;Gage & Quastel, 1966;Hubbard, Jones & Landau, 1968a), so quads are probably not required for the spontaneous release of transmitter. It seems likely, therefore, that quads are only associated with the influx of calcium into a nerve terminal through depolarization-activated calcium 'channels '.…”

The prejunctional actions of some non‐depolarizing blocking drugs

“…Lowering the sodium ion concentration in the Ringer solution decreases the rate of refilling of the store and the size of the available store but produces an increase in the fractional release (Blaber, 1970). It was assumed that the increase in fractional release was due to the removal of sodium ions competing with calcium ions for entry into the nerve terminal (Birks & Cohen, 1965;Kelly, 1965;Gage & Quastel, 1966;Birks, Burstyn & Firth, 1968). It might be expected that local anaesthetics which prevent the entry of sodium ions (Taylor, 1959) would also reduce the rate of refilling of the store and the size of the available store.…”

Ca2+‐independent regulation of neurosecretion by intracellular Na+

“…Although often overlooked, a number of studies on neurotransmitter/neurohormone release have indicated that conditions which raise [Na+]i in nerve endings result in an increased release [6,9,10,27]. Tiffs was evidenced either by an increased frequency in spontaneous miniature excitatory post-synaptic potentials [10, 26,[28][29][30] or by potentiation of evoked responses [4,6,8,23,24].…”

“…However, in a number of neuronal preparations, prolonged high-frequency stimulation results in a potentiation of neurosecretion [2][3][4][5][6] that has been linked to increased intracellular sodium. In each case, the sodium-dependent potentiation of" release has been attributed to either sodium-induced calcium release from intracellular stores [4,7,8] or to enhancement of sodium-calcium exchange [9][10][11]. Until now, little or no attention has been paid to the possibility of a direct action of sodium on exocytosis.…”