Calcium permeability of the nicotinic acetylcholine receptor: the single-channel calcium influx is significant

Abstract

The calcium permeability of the mouse muscle nicotinic ACh receptor (nAChR) was determined using patch-clamp techniques. Single-channel currents were measured in pure external calcium and in mixtures of calcium with cesium or sodium. At low concentrations, calcium decreases the current carried by the monovalent cation. At higher concentrations, calcium displaces the monovalent cation as the main current carrier. In pure external calcium, the conductance of the nAChR is similar to the conductance of the NMDA receptor or the L-type Ca channel. With pure 110-mM calcium as the external cation, the slope conductance of the nAChR channel at negative potentials is 12 pS. An ion-permeation model based on the structure and function of the channel describes the currents. The ion-permeation model predicts that calcium contributes about 2% of the total inward current through a nAChR channel in physiologic solution. The current is about 7% of the calcium current through an L-type Ca channel. Because nAChRs are densely packed at the neuromuscular end plate, the calcium influx at an active synapse is expected to produce a locally high-calcium environment.

Nicotinic Acetylcholine Receptors

“…This is in agreement with estimates that calcium ions carry approximately 2% and 4% of the total nicotinic current through embryonic and adult muscle receptors, respectively (at physiological calcium concentrations and holding potentials; Decker & Dani, 1990;Vernino et al, 1994;Ragozzino et al, 1998)). …”

Modulation of glycine affinity for NMDA receptors by extracellular Ca2+ in trigeminal neurons

“…As in NMDA receptor channels, nACh receptor channels have high Ca2+ permeability (Decker and Dani, 1990;Mulle et al, 1992a,b;Vernino et al, 1992). In observations similar to ours, external Ca2+ potentiates nACh-activated currents and, at the same time, decreases the single nACh receptor channel conductance (Decker and Dani, 1990;Mulle et al, 1992a,b;Vernino et al, 1992). The nACh responses are more sensitive to the change in [Ca*+],.…”

“…For example, Mg" readily permeates through nACh channels (Decker and Dani, 1990) but is largely blocked in NMDA channels (Mayer et al, 1984;Nowak et al, 1984;Mayer and Westbrook, 1987a;Jahr and Stevens, 1990). Barium (Ba2' ) potentiates nACh-activated currents (Mulle et al, 1992b) whereas it reduces the I,,,, (Fig.…”

About the morphological relationships of the sarcoplasmic reticulum in the sole plate area of the frog

“…But an increase of the Ca 2+ -concentration must be buffered rapidly, on the one hand to counteract a desensitisation of acetylcholine receptors (Miledi, 1980), on the other hand to restrict the influence of the liberated Ca 2+ to the metabolism (Decker and Dani, 1990;Zucker, 1985). In those MEP areas of frogs with proximity between subsynaptic folds and myofibrils a fast uptake of the influxed Ca 2+ through the myofibrillar SR is to be expected because of short diffusion distances.…”