Biochemistry and Molecular Biology - Belyasova N.A. 2002

Structure and Functions of Cellular Components
Biomembranes
Generation and Conduction of Nerve Impulses

Due to the continuous activity of membrane ion pumps, a constant potential difference is maintained between the interior of a resting Cell and its external environment. This parameter can be measured by inserting an electrode into large Nerve Cells, which in squids, for instance, can reach a diameter of 1 mm. The measured value is referred to as the Resting Potential and typically ranges from (-60) to (-70) mV in unexcited cells (the minus sign indicates that the inner surface of the membrane is electronegative relative to the outer surface). The resting potential reflects a state of dynamic equilibrium in the Transmembrane Movement of sodium and potassium ions.

When a membrane site is stimulated by an electric current or another stimulus, specific sodium channels open at that Location, and Na⁺ ions rush inward, neutralizing the negative charge on the inner surface of the membrane. This phenomenon is known as depolarization. If the threshold of the triggering stimulus is sufficiently high (greater than 10 mV), Voltage-Gated Sodium Channels open to generate an Action Potential. An action potential is an impulse that propagates along the nerve cell membrane, altering the Membrane Potential in a fraction of a millisecond (approximately 0.5 ms in mammalian nerves). The key Features of the action potential are its high conduction velocity along the nerve cell membrane—up to 100 m/s—and its constant amplitude.

The Mechanism of Nerve Impulse transmission is as follows. The increase in membrane permeability to sodium ions at a specific site and the resulting depolarization mutually reinforce one another. Due to the rapid influx of sodium ions to the inner surface of the membrane, the initial resting potential (-70 mV) drops to zero and then reaches (+20) to (+40) mV. Consequently, a region of positive charge is created at this membrane site, and a local current flows between this active area and the negatively charged region immediately ahead of it. A distinctive feature of nerve cell membranes that conduct impulses very rapidly is the presence of a myelin sheath, which acts as an insulator. Because of this sheath, The Plasma Membrane contacts the Na⁺-containing extracellular fluid only at specific points known as the nodes of Ranvier, and membrane depolarization occurs exclusively at these nodes. Since the nerve cell is insulated by myelin, the spread of the electrical current to the next node occurs primarily through the Cell Cytoplasm. Upon reaching the subsequent node, the current lowers the membrane potential in that area, triggering depolarization and increasing sodium ion permeability—thus generating an action potential. In this manner, the action potential propagates unidirectionally along the membrane as a wave of depolarization.

Repolarization occurs as K⁺ ions flow out of the axon. Until repolarization is complete, the node cannot be re-excited; by the time the node is ready to respond again, the impulse has already traveled too far along the membrane to reopen the sodium channels at that particular axonal site. For this reason, the impulse propagates in only one direction along the nerve cell membrane. Repolarization concludes once the ATPases involved in Active ion transport restore the normal concentration ratios of Na⁺ and K⁺ at the node.

The amplitude of the action potential is constant for each individual nerve cell and does not decrease as it travels along the membrane, because the changes at each point of the membrane are driven by local energy reserves stored in the ion gradient, even though the process is initiated by the change at the preceding node.

The transmission of nerve impulses between Neurons and from neurons to Muscle cells takes place at nerve endings, or synapses, via signaling molecules known as Neurotransmitters. One of the most widespread neurotransmitters (synthesized by nerve cells) is acetylcholine. The release of acetylcholine by synaptic membranes signals the generation of a nerve impulse in the adjacent nerve cell. This process is mediated by acetylcholine receptors, which are transmembrane complexes consisting of five subunits that form a channel permeable to Na⁺ and K⁺ ions.

The binding sites for acetylcholine are located on the extracellular portion of the a-subunit of the receptor. Their occupation triggers an allosteric conformational change in the charged Regions of the receptor's polypeptide chains, transiently opening the central transmembrane channel for the passage of sodium and potassium ions. The opening and closing of the channel result from allosteric shifts in the charged areas of the receptor's polypeptide chains. The transmembrane movement of ions alters the resting potential of the nerve or muscle cell, which in turn stimulates the opening of voltage-gated Na channels, thereby generating an action potential.

The Acetylcholine Receptor can bind various pharmacological agents, such as nicotine, which activates acetylcholine receptors at low doses and inhibits them at high doses. In addition, many snake neurotoxins are capable of interacting with the acetylcholine receptor and disrupting its function. Another well-known phenomenon is the competitive inhibition of acetylcholine binding to the receptor by curare (a plant alkaloid), which South American indigenous peoples used to coat their arrowheads.