flowing inwards at a point on the axon during an action potential spread out along the axon, and depolarize the adjacent sections of its membrane. if sufficiently strong, this depolarization provokes a similar action potential at the neighboring membrane patches. this basic mechanism was demonstrated by alan lloyd hodgkin in 1937. after crushing or cooling nerve segments and thus blocking the action potentials, he showed that an action potential arriving on one side of the block could provoke another action potential on the other, provided that the blocked segment was sufficiently short. once an action potential has occurred at a patch of membrane, the membrane patch needs time to recover before it can fire again. at the molecular level, this absolute refractory period corresponds to the time required for the voltage-activated sodium channels to recover from inactivation, i.e., to return to their closed state. there are many types of voltage-activated potassium channels in neurons. some of them inactivate fast (a-type currents) and some of them inactivate slowly or not inactivate at all; this variability guarantees that there will be always an available source of current for repolarization, even if some of the potassium channels are inactivated because of preceding depolarization. on the other hand, all neuronal voltage-activated sodium channels inactivate within several milliseconds during strong depolarization, thus making following depolarization impossible until a substantial fraction of sodium channels have returned to their closed state. although it limits the frequency of firing, the absolute refractory period ensures that the action potential moves in only one direction along an axon. the currents flowing in due to an action potential spread out in both directions along the axon. however, only the unfired part of the axon can respond with an action potential; the part that has just fired is unresponsive until the action potential is safely out of range and cannot restimulate that part. in the usual orthodromic conduction, the action potential propagates from the axon hillock towards the synaptic knobs (the axonal termini); propagation in the opposite direction—known as antidromic conduction—is very rare. however, if a laboratory axon is stimulated in its middle, both halves of the axon are "fresh", i.e., unfired; then two action potentials will be generated, one traveling towards the axon hillock and the other traveling towards the synaptic knobs. myelin and saltatory conduction main articles: myelination and saltatory conduction in saltatory conduction, an action potential at one node of ranvier causes inwards currents that depolarize the membrane at the next node, provoking a new action potential there; the action potential appears to "hop" from node to node. in order to enable fast and efficient transduction of electrical signals in the nervous system, certain neuronal axons are covered with myelin sheaths. myelin is a multilamellar membrane that enwraps the axon in segments separated by intervals known as nodes of ranvier. it is produced by specialized cells: schwann cells exclusively in the peripheral nervous system, and oligodendrocytes exclusively in the central nervous system. myelin sheath reduces membrane capacitance and increases membrane resistance in the inter-node intervals, thus allowing a fast, saltatory movement of action potentials from node to node. myelination is found mainly in vertebrates, but an analogous system has been discovered in a few invertebrates, such as some species of shrimp. not all neurons in vertebrates are myelinated; for example, axons of the neurons comprising the autonomous nervous system are not, in general, myelinated. myelin prevents ions from entering or leaving the axon along myelinated segments. as a general rule, myelination increases the conduction velocity of action potentials and makes them more energy-efficient. whether saltatory or not, the mean conduction velocity of an action potential ranges from 1 meter per second (m/s) to over 100 m/s, and, in general, increases with axonal diameter. action potentials cannot propagate through the membrane in myelinated segments of the axon. however, the current is carried by the cytoplasm, which is sufficient to depolarize the first or second subsequent node of ranvier. instead, the ionic current from an action potential at one node of ranvier provokes another action potential at the next node; this apparent "hopping" of the action potential from node to node is known as saltatory conduction. although the mechanism of saltatory conduction was suggested in 1925 by ralph lillie, the first experimental evidence for saltatory conduction came from ichiji tasaki and taiji takeuchi and from andrew huxley and robert stämpfli. by contrast, in unmyelinated axons, the action potential provokes another in the membrane immediately adjacent, and moves continuously down the axon like a wave. comparison of the conduction velocities of myelinated and unmyelinated axons in the cat. the conduction velocity v of myelinated neurons varies roughly linearly with axon diameter d (that is, v ∝ d), whereas the speed of unmyelinated neurons varies roughly as the square root (v ∝√d). the red and blue curves are fits of experimental data, whereas the dotted lines are their theoretical extrapolations. myelin has two important advantages: fast conduction speed and energy efficiency. for axons larger than a minimum diameter (roughly 1 micrometre), myelination increases the conduction velocity of an action potential, typically tenfold. conversely, for a given conduction velocity, myelinated fibers are smaller than their unmyelinated counterparts. for example, action potentials move at roughly the same speed (25 m/s) in a myelinated frog axon and an unmyelinated squid giant axon, but the frog axon has a roughly 30-fold smaller diameter and 1000-fold smaller cross-sectional area. also, since the ionic currents are confined to the nodes of ranvier, far fewer ions "leak" across the membrane, saving metabolic energy. this saving is a significant selective advantage, since the human nervous system uses approximately 20% of the body's metabolic energy. the length of axons' myelinated segments is important to the success of saltatory conduction. they should be as long as possible to maximize the speed of conduction, but not so long that the arriving signal is too weak to provoke an action potential at the next node of ranvier. in nature, myelinated segments are generally long enough for the passively propagated signal to travel for at least two nodes while retaining enough amplitude to fire an action potential at the second or third node. thus, the safety factor of saltatory conduction is high, allowing transmission to bypass nodes in case of injury. however, action potentials may end prematurely in certain places where the safety factor is low, even in unmyelinated neurons; a common example is the branch point of an axon, where it divides into two axons. some diseases degrade myelin and impair saltatory conduction, reducing the conduction velocity of action potentials. the most well-known of these is multiple sclerosis, in which the breakdown of myelin impairs coordinated movement. cable theory main article: cable theory cable theory's simplified view of a neuronal fiber. the connected rc circuits correspond to adjacent segments of a passive neurite. the extracellular resistances re (the counterparts of the intracellular resistances ri) are not shown, since they are usually negligibly small; the extracellular medium may be assumed to have the same voltage everywhere. the flow of currents within an axon can be described quantitatively by cable theory and its elaborations, such as the compartmental model. cable theory was developed in 1855 by lord kelvin to model the transatlantic telegraph cable and was shown to be relevant to neurons by hodgkin and rushton in 1946. in simple cable theory, the neuron is treated as an electrically passive, perfectly cylindrical transmission cable, which can be described by a partial differential equation τ ∂ v ∂ t = λ 2 ∂ 2 v ∂ x 2 − v =\lambda ^v}-v} where v(x, t) is the voltage across the membrane at a time t and a position x along the length of the neuron, and where λ and τ are the characteristic length and time scales on which those voltages decay in response to a stimulus. referring to the circuit diagram on the right, these scales can be determined from the resistances and capacitances per unit length. τ = r m c m c_\,} λ = r m r ℓ these time and length-scales can be used to understand the dependence of the conduction velocity on the diameter of the neuron in unmyelinated fibers. for example, the time-scale τ increases with both the membrane resistance rm and capacitance cm. as the capacitance increases, more charge must be transferred to produce a given transmembrane voltage (by the equation q = cv); as the resistance increases, less charge is transferred per unit time, making the equilibration slower. in a similar manner, if the internal resistance per unit length ri is lower in one axon than in another (e.g., because the radius of the former is larger), the spatial decay length λ becomes longer and the conduction velocity of an action potential should increase. if the transmembrane resistance rm is increased, that lowers the average "leakage" current across the membrane, likewise causing λ to become longer, increasing the conduction velocity. termination chemical synapses main articles: chemical synapse, neurotransmitter, excitatory postsynaptic potential, and inhibitory postsynaptic potential in general, action potentials that reach the synaptic knobs cause a neurotransmitter to be released into the synaptic cleft. neurotransmitters are small molecules that may open ion channels in the postsynaptic cell; most axons have the same neurotransmitter at all of their termini. the arrival of the action potential opens voltage-sensitive calcium channels in the presynaptic membrane; the influx of calcium causes vesicles filled with neurotransmitter to migrate to the cell's surface and release their contents into the synaptic cleft. this complex process is inhibited by the neurotoxins tetanospasmin and botulinum toxin, which are responsible for tetanus and botulism, respectively. electrical synapses between excitable cells allow ions to pass directly from one cell to another, and are much faster than chemical synapses. electrical synapses main articles: electrical synapse, gap junction, and connexin some synapses dispense with the "middleman" of the neurotransmitter, and connect the presynaptic and postsynaptic cells together. when an action potential reaches such a synapse, the ionic currents flowing into the presynaptic cell can cross the barrier of the two cell membranes and enter the postsynaptic cell through pores known as connexons. thus, the ionic currents of the presynaptic action potential can directly stimulate the postsynaptic cell. electrical synapses allow for faster transmission because they do not require the slow diffusion of neurotransmitters across the synaptic cleft. hence, electrical synapses are used whenever fast response and coordination of timing are crucial, as in escape reflexes, the retina of vertebrates, and the heart. neuromuscular junctions main articles: neuromuscular junction, acetylcholine receptor, and cholinesterase enzyme a special case of a chemical synapse is the neuromuscular junction, in which the axon of a motor neuron terminates on a muscle fiber. in such cases, the released neurotransmitter is acetylcholine, which binds to the acetylcholine receptor, an integral membrane protein in the membrane (the sarcolemma) of the muscle fiber. however, the acetylcholine does not remain bound; rather, it dissociates and is hydrolyzed by the enzyme, acetylcholinesterase, located in the synapse. this enzyme quickly reduces the stimulus to the muscle, which allows the degree and timing of muscular contraction to be regulated delicately. some poisons inactivate acetylcholinesterase to prevent this control, such as the nerve agents sarin and tabun, and the insecticides diazinon and malathion. other cell types cardiac action potentials main articles: cardiac action potential, electrical conduction system of the heart, cardiac pacemaker, and heart arrhythmia phases of a cardiac action potential. the sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing eflux of potassium ions. the characteristic plateau ("2") results from the opening of voltage-sensitive calcium channels. the cardiac action potential differs from the neuronal action potential by having an extended plateau, in which the membrane is held at a high voltage for a few hundred milliseconds prior to being repolarized by the potassium current as usual. this plateau is due to the action of slower calcium channels opening and holding the membrane voltage near their equilibrium potential even after the sodium channels have inactivated. the cardiac action potential plays an important role in coordinating the contraction of the heart. the cardiac cells of the sinoatrial node provide the pacemaker potential that synchronizes the heart. the