Lecture 8 Conduction of nerve impulse The impulse is conducted throughout the neuron by one of two methods of propagation:contiguous conduction or saltatory conduction. Contiguous conduction involves the spread of the action potential along every patch of membrane down the length of the axon (fig.1), which represents a longitudinal section of the axon hillock and the portion of the axon immediately beyond it.
Figure 1 Contiguous conduction. Local current flow between the active area at the peak of an action potential and the adjacent inactive area still at resting potential reduces the potential in this contiguous inactive area to threshold, which triggers an action potential in the previously inactive area. The original active area returns to resting potential, and the new active area induces an action potential in the next adjacent inactive area by local current flow as the cycle repeats itself down the length of the axon. Refractory periods a- Absolute refractory period is the period during which another action potential cannot be elicited, no matter how large the stimulus. coincides with almost the entire duration of the action potential. Explanation: Recall that the inactivation gates of the Na+ channels are closed when the membrane potential is depolarized. They remain closed until repolarization occurs. No action potential can occur until the inactivation gates open. b-Relative refractory period begins at the end of the absolute refractory period and continues until the membrane potential returns to the resting level. An action potential can be elicited during this period only if a larger than usual inward current is provided. Explanation: The K+ conductance is higher than at rest, and the membrane potential is closer to the K+ equilibrium potential and, therefore, farther from threshold; more inward current is required to bring the membrane to threshold.(see fig. 2, and fig. 3)
Figure 2 Value of the refractory period. The refractory period prevents “backward” current flow. During an action potential and slightly afterward, an area cannot be restimulated by normal events to undergo another action potential. Thus, the refractory period ensures that an action potential can be propagated only in the forward direction along the axon.
Figure 3 Absolute and relative refractory periods. During the absolute refractory period, the portion of the membrane that has just undergone an action potential cannot be restimulated. This period corresponds to the time during which the Na gates are not in their resting conformation. During the relative refractory period, the membrane can be restimulated only by a stronger stimulus than is usually necessary. This period corresponds to the time during which the K gates opened during the action potential have not yet closed, coupled with lingering inactivation of the voltage gated Na channels. Action potentials occur in all or none fashion an excitable membrane either responds to a triggering event with a maximal action potential that spreads non decrementally throughout the membrane, or it does not respond with an action potential at all. This property is called the all-or-none law. Myelination increases the speed of conduction of action potentials Myelinated fibers are axons covered with myelin, a thick layer composed primarily of lipids, at regular intervals along their length (fig. 4a). Because the water-soluble ions responsible for carrying current across the membrane cannot permeate this myelin coating, it acts as an insulator, prevent leakage of current across the myelinated portion of the membrane. Myelin is not actually a part of the neuron but consists of separate myelin-forming cells that wrap themselves around the axon. These myelin forming cells are Schwann cells in the peripheral nervous system (PNS) (fig. 4b), the nerves running between the CNS and the various regions of the body, and oligodendrocytes in the CNS (the brain and spinal cord) (fig. 4c).
Figure 4 Myelinated fibers. (a) A myelinated fiber is surrounded by myelin at regular intervals. The intervening bare, unmyelinated regions are known as nodes of Ranvier. The electron micrograph shows a myelinated fiber in cross section at a myelinated region. (b) In the PNS each patch of myelin is formed by a separate Schwann cell that wraps itself jelly-roll fashion around the nerve fiber. (c) In the CNS each of the several processes (“arms”) of a myelin-forming oligodendrocyte forms a patch of myelin around a separate nerve fiber. Between the myelinated regions, at the nodes of Ranvier, the axonal membrane is bare and exposed to the ECF. Current can flow across the membrane only at these bare spaces to produce action potentials. Voltage-gated Na channels are concentrated at the nodes, whereas the myelin-covered regions are almost devoid of these special passage ways.The distance between the nodes is short enough that local current can flow between an active node and an adjacent inactive node before dying off. In a myelinated fiber, the impulse “jumps” from node to node, skipping over the myelinated sections of the axon (fig. 5); this process is called saltatory conduction (saltare means “to jump or leap”). Saltatory conduction propagates action potentials more rapidly than contiguous conduction does, because the action potential does not have to be regenerated at myelinated sections but must be regenerated within every section of an unmyelinated axonal membrane from beginning to end.
Figure 5 Saltatory conduction. The impulse “jumps” from node to node in a myelinated fiber. Synapses There are two types of synapses: electrical synapses and chemical synapses. in electrical synapse, two neurons are connected by gap junctions, which allow charge carrying ions to flow directly between the two cells in either direction. in chemical synapses a chemical messenger transmits information one way across a space separating the two neurons. A chemical synapse involves a junction between an axon terminal of one neuron, known as the presynaptic neuron, and the dendrites or cell body of a second neuron, known as the postsynaptic neuron. The dendrites and, to a lesser extent, the cell body of most neurons receive thousands of synaptic inputs, which are axon terminals from many other neurons. Some neurons in the CNS receive as many as 100,000 synaptic inputs (fig. 6). The anatomy of one of these thousands of chemical synapses is shown in fig. 7. The anatomy of one of these thousands of chemical synapses is shown in fig. 7.
Figure 6 Synaptic inputs (presynaptic axon terminals) to the cell body and dendrites of a single postsynaptic neuron. The drying process used to prepare the neuron for the electron micrograph has toppled the presynaptic axon terminals and pulled them away from the postsynaptic cell body. A neurotransmitter carries the signal across a synapse When an action potential in a presynaptic neuron has been propagated to the axon terminal (fig.7), the sequence of events take place at a synapse. The permeability change induced at an excitatory synapse results in the movement of a few K ions out of the postsynaptic neuron, while a larger number of Na ions simultaneously enter this neuron. The result is net movement of positive ions into the cell. This makes the inside of the membrane slightly less negative than at resting potential, thus producing a small epolarization of the postsynaptic neuron.
Figure 7 Structure and function of a single synapse. The numbered steps designate the sequence of events that take place at a synapse. The blowup depicts the release by exocytosis of neurotransmitter from the presynaptic axon terminal and its subsequent binding with receptors specific for it on the subsynaptic membrane of the postsynaptic neuron. The electron micrograph shows a synapse between a presynaptic axon terminal and a dendrite of a postsynaptic cell. There are two types of synapses, depending on the permeability changes induced in the postsynaptic neuron by the combination of a specific neurotransmitter with its receptor-channels: excitatory synapses and inhibitory synapses. Excitatory synapses, At an excitatory synapse, the response to the binding of a neurotransmitter to the receptor-channel is the opening of nonspecific cation channels in the subsynaptic membrane that permit simultaneous passage of Na and K through them. Activation of one excitatory synapse can rarely depolarize the postsynaptic neuron enough to bring it to threshold. the change in postsynaptic potential occurring at an excitatory synapse is called an excitatory postsynaptic potential, or EPSP (fig.8a).
(a) Excitatory synapse Inhibitory synapses, At an inhibitory synapse, the binding of a different released neurotransmitter with its receptor-channels increases the permeability of the subsynaptic membrane to either K or Cl. The resulting ion movements typically bring about a small hyperpolarization of the postsynaptic neuron—that is, the inside of the neuron becomes slightly more negative (fig.8b).
(b) Inhibitory synapse Figure 8 Postsynaptic potentials. (a) An excitatory postsynaptic potential (EPSP) brought about by activation of an excitatory presynaptic input brings the postsynaptic neuron closer to threshold potential. (b) An inhibitory postsynaptic potential (IPSP) brought about by activation of an inhibitory presynaptic input moves the postsynaptic neuron farther from threshold potential. The grand postsynaptic potential depends on the sum of activities of the presynaptic inputs EPSPs and IPSPs are graded potentials. Unlike action potentials, which behave according to the all-or-none law, graded potentials can be of varying magnitude, have no refractory period, and can be summed (added on top of one another). What are the mechanisms and significance of summation? Temporal summation, Suppose that Ex1 has an action potential that causes an EPSP in the postsynaptic neuron. After this EPSP has died off, if another action potential occurs in Ex1, an EPSP of the same magnitude takes place before dying off (fig.9). Spatial summation, Let us now see what happens in the postsynaptic neuron if both excitatory inputs are stimulated simultaneously (fig.9).
Figure 9 Determination of the grand postsynaptic potential by the sum of activity in the presynaptic inputs. Two excitatory (Ex1 and Ex2) and one inhibitory (In1) presynaptic inputs terminate on this hypothetical postsynaptic neuron. The potential of the postsynaptic neuron is being recorded. For simplicity in the figure, summation of two EPSPs brings the postsynaptic neuron to threshold, but in reality many EPSPs must sum to reach threshold
Dr. Karim R. Hamad