Cell signalling
Cell signalling

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Cell signalling

2.3.1 Ion-channel receptors

Nicotinic cholinergic receptors are probably the best studied of all receptors, firstly because they are present throughout skeletal muscle, and secondly because there are plenty of natural and synthetic toxins that bind specifically to this receptor. Furthermore, the technique of patch-clamp electrophysiology has made possible the detailed characterization of the properties of individual ion channels (Figure 21a).

Figure 21 (a) The technique of patch-clamp recording. A small fire-polished glass micropipette is pressed against the plasma membrane of a skeletal muscle cell, forming a tight seal. The voltage of the plasma membrane is fixed, and the current through individual ion channels is then measured using a metal electrode inserted in the glass micropipette in an electrolyte salt solution and (d) Structure of the nicotinic acetylcholine receptor in the form of electron-density contour maps; (c) and (e) diagrammatic representations of the receptor. (b) and (c) show the barrel shape of the receptor ‘from above’, comprising five subunits around a central pore. (d) and (e) show the receptor in cross-section. There are binding sites for two acetylcholine molecules, one on the channel side of each a subunit. Further down, the pore is shaped by a ring of bent a-helical rods (indicated as bars), forming a gate ((d) is shown in the closed position). On binding of acetylcholine, the receptor undergoes a conformational change, which opens the gate (as in (e)), allowing the entry of Na+ions into the cell and the exit of K+ions.

Nicotinic receptors are composed of five subunits (two α subunits together with one each of the β, γ and δ subunits), which assemble to form a pore in the membrane (Figure 21b–e). The pore can switch between an open and a closed state on binding of two molecules of acetylcholine to the two α subunits at sites within the channel (Figure 21). Although the channel alternates between an open and a closed state, binding of acetylcholine increases the probability of the channel being in its open state. When the channel is open, sodium ions flow into the muscle cell, using concentration and voltage gradients. The influx of positive charge due to the Na+ions inside the cell tends to locally neutralize the negative charge inside the cell (called ‘depolarization’). The channel is also permeable to K+ions, which exit the cell. However, the overall effect of the movement of ions causes the net charge inside the cell with respect to the outside to become more positive, and this is ultimately responsible for skeletal muscle contraction (Figure 7).

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