BIOG 1105-1106 | Cornell Introductory Biology, Individualized Instruction

If impulse conduction involves inward flow of Na+ ions followed by outward flow of K+ ions, how does the neuron reestablish its original ionic balance? In other words, how does it get rid of the extra Na+ ions and regain the lost K+ ions? If the initial ionic distribution were not restored, the neuron would lose its ability to conduct impulses. But, we know that a normal neuron can continue to conduct impulses indefinitely, with only a very brief refractory period (on the order of 0.5 to 2 milliseconds) after each impulse, during which time it cannot be stimulated.

Two mechanisms work to keep neurons functioning: (1) diffusion and electrostatic attraction, and (2) a sodium-potassium exchange pump. In the short run, as an impulse passes and the membrane is depolarized, diffusion restores the electrochemical balance between Na+ ions outside and K+ ions inside the cell almost instantaneously. To understand how this happens, it is important to realize that virtually all events involving the action potential take place very close to the cell membrane. In a resting nerve fiber, the free ions that have been attracted to the cell membrane by the opposite charges on the other side turn that part of the membrane into an area of concentrated charge; the electrostatic gradient across the thin membrane approaches an incredible 105 v/cm. Once the two surfaces of the membrane have been “coated” by ions attracted to the electrostatic force of the oppositely charged ions on the other side, this concentrated layer of charge repels the approach of additional ions from the same side (see Figure below).

Charging of the membrane. (A.-B.) Electrostatic attraction across the cell membrane draws some of the positive ions on the outside and some of the negative ions on the inside to the respective surfaces of the membrane. C. As a result, these surfaces become coated with oppositely charged ions. At some point, however, no more ions are attracted: the concentration of positive ions on the outer surface is so high that electrostatic forces repel the free-floating positive ions to the same degree as those ions are attracted to the negatively charged interior of the cell. On the other side of the membrane an equivalent situation develops with respect to negative ions.

When an action potential allows ions to cross the membrane, only the ion concentrations near the highly charged inner and outer surfaces of the membrane are affected, simply because the permeability changes are so short-lived that only the closest ions have time to move to and through the membrane. The tiny resulting alteration in ion concentration is rapidly absorbed as the Na+ ions that crossed into the neuron, and the K+ ions that moved out, diffuse into the fluid on either side of the membrane. It is rather like adding a drop of ink to a pond: for a moment there is a dark patch, but it soon dissipates as the ink diffuses into the larger volume of water. The rapid diffusion of the small number of ions involved into the relatively enormous volume of the cell and the extracellular fluid allows the intense local electrostatic gradient at the cell membrane to reestablish itself almost immediately.

Despite the dramatic nature of the events at the neural membrane, in reality only minute quantity—about 10^-12 moles— of Na+ ions enter the cell during an action potential. The net effect of a single action potential on the movement of Na+ ions inside the cell as a whole is therefore negligible. The reserve of ions both inside and out is so large that a recently killed neuron will continue to conduct action potentials for some time. Eventually, however, the action potentials begin to deteriorate and conduction comes to a halt. If we were to continue polluting our pond with ink, at some point it would begin to change color. Similarly, at some point the internal fluid of the nerve cell can no longer sufficiently dilute the doses of Na+ ions that have been repeatedly allowed to enter, and replace K+ ions. In the long run, however, the potential will decline if the Na+ that enters is not removed and the K+ that leaves is not recovered. Because expelling the Na+ ions means moving them against their concentration and electrical gradients, and likewise regaining the lost K+ ions means transporting them against their gradients, the neuron must carry out active transport, which requires energy. It has been demonstrated that the membrane of the neuron incorporates an ATP-driven sodium-potassium exchange pump. We know now that the membrane of the average neuron contains approximately a million sodium-potassium exchange pumps, and that their power is supplied by ATP. In fact, the sodium- potassium pumps are major energy-users in the cells of the human body; about 33 percent of the energy consumed is used to fuel these pumps. Such pumps enable cells to actively extrude Na+ ions and take up K+ ions. The development of sodium-potassium pumps, combined with the evolution of ion-specific voltage-gated channels, is the basis for the evolution of neural transmission.

The ions that cross the neural membrane during an action potential rapidly diffuse away from the membrane into the abundant fluid inside and outside the cell. (A) Before the Na+ channel shown here opens in response to partial membrane depolarization, the membrane is fully charged. (B) When the gate opens, Na+ ions rush into the cell, reducing and then reversing the electrostatic gradient across the membrane. (C) After the channel closes, the excess Na+ near the inner membrane of the neuron rapidly diffuses into the cytosol, and the membrane begins to recharge.

Plant cells are actually very well suited for producing electrical signals. Recall that plant cells are connected to one another through their plasmodesmata, and that their cytoplasm is continuous. Consequently, an electrical signal produced in one cell, usually a parenchyma cell, can spread easily to others. That plants can produce an action potential in response to touch, wounding, cold shock, or infection has been known for many years, but whether the action potential conveys information and elicits a response is controversial. Recently, however, evidence has been accumulating that the electrical signals produced in response to wounding do have a signaling role, at least in some plants. Damaging the cotyledon (seed leaf) of a tomato seedling results in the production of an action potential that travels from the cotyledon along the stem to the first leaf where it activates the wound response genes. In plants, as in animals, the action potential is due to specific ions, often calcium or hydrogen ions, rushing into and out of the cell. It is relatively slow, 1 to 4 mm per second, compared to 100 meters per second in some human axons. In tomato seedlings, the action potential appears to activate the wound response genes in target cells and the cells begin producing defensive proteins. Chilling the stem prevents phloem transport, but not the action potential or the response, suggesting that it is the action potential, not a chemical signal transported through the phloem, that induces the wounding response. Many investigators, however, doubt the signaling value of electrical activity in plants, and the subject remains an area of active research.

Chemical synapses result in one-way transmission of impulses along the neural pathways even though an individual neuron can conduct impulses in both directions. If, for example, we stimulate an axon at a point between its base and its terminus, an impulse will move in both directions along the axon from the point of stimulation. But the impulse moving back toward the cell body and dendrites will die when it reaches the end of the cell; it cannot bridge the gap to the next cell because dendrites cannot release transmitter chemicals. Only the synaptic terminals of axons secrete transmitters, so impulses can only go from synaptic terminals of the axon to the next neuron.

Because of the time it takes for a neurotransmitter to be released, diffuse across the cleft, interact with receptors, and affect a response in the postsynaptic neuron, chemical synapses are much slower than electrical synapses or impulse transmission along the neuron itself. The synaptic delay is proportional to the number of synapses involved; the more chemical synapses in a pathway, the longer it takes for information to be received, transmitted, and processed.

The story of impulse transmission does not end with the diffusion of transmitter across the cleft. If the transmitter remained, the postsynaptic receptors would be stimulated indefinitely by the arrival of a single action potential; a mechanism to remove the transmitter is therefore required. Some transmitters simply diffuse away from the synaptic cleft, others, such as norepinephrine, are taken back up for reuse by the presynaptic neuron, and still others are destroyed by specific enzymes. For example, the transmitter acetylcholine is removed from the synapse by an enzyme called cholinesterase. By destroying the transmitter, this enzyme makes it possible for the next impulse, with new information, to be transmitted. Many insecticides, such as the organophosphates (also known as nerve gases), are cholinesterase inhibitors. They block the enzymatic destruction of acetylcholine, with the predictable result that an insect exposed to them becomes permanently active. Given in high enough doses, acetylcholinerase inhibitors will paralyze and kill an animal.

The normal resting potential of a typical neuron is about –70 mv. An excitatory transmitter substance slightly reduces that polarization – that is, makes the inner surface of the membrane less strongly negative – thereby creating an excitatory postsynaptic potential (EPSP). If the EPSP reaches the threshold level (usually about –50 mv), an impulse (action potential) is triggered. If the transmitter substance had been inhibitory, the membrane could have become hyperpolarized (to perhaps –75 mv), a condition called an inhibitory postsynaptic potential (IPSP) (dashed curve), and no action potential would have resulted; the neuron would slowly have returned to its resting potential after release of the transmitter had ceased.