potentials from several synapses must work together at nearly the same time to provoke a new action potential. their joint efforts can be thwarted, however, by the counteracting inhibitory postsynaptic potentials. neurotransmission can also occur through electrical synapses. due to the direct connection between excitable cells in the form of gap junctions, an action potential can be transmitted directly from one cell to the next in either direction. the free flow of ions between cells enables rapid non-chemical-mediated transmission. rectifying channels ensure that action potentials move only in one direction through an electrical synapse. electrical synapses are found in all nervous systems, including the human brain, although they are a distinct minority. "all-or-none" principle the amplitude of an action potential is often thought to be independent of the amount of current that produced it. in other words, larger currents do not create larger action potentials. therefore, action potentials are said to be all-or-none signals, since either they occur fully or they do not occur at all. this is in contrast to receptor potentials, whose amplitudes are dependent on the intensity of a stimulus. in both cases, the frequency of action potentials is correlated with the intensity of a stimulus. despite the classical view of the action potential as a stereotyped, uniform signal having dominated the field of neuroscience for many decades, newer evidence does suggest that action potentials are more complex events indeed capable of transmitting information through not just their amplitude, but their duration and phase as well, sometimes even up to distances originally not thought to be possible. sensory neurons main article: sensory neuron in sensory neurons, an external signal such as pressure, temperature, light, or sound is coupled with the opening and closing of ion channels, which in turn alter the ionic permeabilities of the membrane and its voltage. these voltage changes can again be excitatory (depolarizing) or inhibitory (hyperpolarizing) and, in some sensory neurons, their combined effects can depolarize the axon hillock enough to provoke action potentials. some examples in humans include the olfactory receptor neuron and meissner's corpuscle, which are critical for the sense of smell and touch, respectively. however, not all sensory neurons convert their external signals into action potentials; some do not even have an axon. instead, they may convert the signal into the release of a neurotransmitter, or into continuous graded potentials, either of which may stimulate subsequent neuron(s) into firing an action potential. for illustration, in the human ear, hair cells convert the incoming sound into the opening and closing of mechanically gated ion channels, which may cause neurotransmitter molecules to be released. in similar manner, in the human retina, the initial photoreceptor cells and the next layer of cells (comprising bipolar cells and horizontal cells) do not produce action potentials; only some amacrine cells and the third layer, the ganglion cells, produce action potentials, which then travel up the optic nerve. pacemaker potentials main article: pacemaker potential in pacemaker potentials, the cell spontaneously depolarizes (straight line with upward slope) until it fires an action potential. in sensory neurons, action potentials result from an external stimulus. however, some excitable cells require no such stimulus to fire: they spontaneously depolarize their axon hillock and fire action potentials at a regular rate, like an internal clock. the voltage traces of such cells are known as pacemaker potentials. the cardiac pacemaker cells of the sinoatrial node in the heart provide a good example. although such pacemaker potentials have a natural rhythm, it can be adjusted by external stimuli; for instance, heart rate can be altered by pharmaceuticals as well as signals from the sympathetic and parasympathetic nerves. the external stimuli do not cause the cell's repetitive firing, but merely alter its timing. in some cases, the regulation of frequency can be more complex, leading to patterns of action potentials, such as bursting. phases the course of the action potential can be divided into five parts: the rising phase, the peak phase, the falling phase, the undershoot phase, and the refractory period. during the rising phase the membrane potential depolarizes (becomes more positive). the point at which depolarization stops is called the peak phase. at this stage, the membrane potential reaches a maximum. subsequent to this, there is a falling phase. during this stage the membrane potential becomes more negative, returning towards resting potential. the undershoot, or afterhyperpolarization, phase is the period during which the membrane potential temporarily becomes more negatively charged than when at rest (hyperpolarized). finally, the time during which a subsequent action potential is impossible or difficult to fire is called the refractory period, which may overlap with the other phases. the course of the action potential is determined by two coupled effects. first, voltage-sensitive ion channels open and close in response to changes in the membrane voltage vm. this changes the membrane's permeability to those ions. second, according to the goldman equation, this change in permeability changes the equilibrium potential em, and, thus, the membrane voltage vm. thus, the membrane potential affects the permeability, which then further affects the membrane potential. this sets up the possibility for positive feedback, which is a key part of the rising phase of the action potential. a complicating factor is that a single ion channel may have multiple internal "gates" that respond to changes in vm in opposite ways, or at different rates. for example, although raising vm opens most gates in the voltage-sensitive sodium channel, it also closes the channel's "inactivation gate", albeit more slowly. hence, when vm is raised suddenly, the sodium channels open initially, but then close due to the slower inactivation. the voltages and currents of the action potential in all of its phases were modeled accurately by alan lloyd hodgkin and andrew huxley in 1952, for which they were awarded the nobel prize in physiology or medicine in 1963. however, their model considers only two types of voltage-sensitive ion channels, and makes several assumptions about them, e.g., that their internal gates open and close independently of one another. in reality, there are many types of ion channels, and they do not always open and close independently. stimulation and rising phase a typical action potential begins at the axon hillock with a sufficiently strong depolarization, e.g., a stimulus that increases vm. this depolarization is often caused by the injection of extra sodium cations into the cell; these cations can come from a wide variety of sources, such as chemical synapses, sensory neurons or pacemaker potentials. for a neuron at rest, there is a high concentration of sodium and chloride ions in the extracellular fluid compared to the intracellular fluid, while there is a high concentration of potassium ions in the intracellular fluid compared to the extracellular fluid. the difference in concentrations, which causes ions to move from a high to a low concentration, and electrostatic effects (attraction of opposite charges) are responsible for the movement of ions in and out of the neuron. the inside of a neuron has a negative charge, relative to the cell exterior, from the movement of k+ out of the cell. the neuron membrane is more permeable to k+ than to other ions, allowing this ion to selectively move out of the cell, down its concentration gradient. this concentration gradient along with potassium leak channels present on the membrane of the neuron causes an efflux of potassium ions making the resting potential close to ek ≈ –75 mv. since na+ ions are in higher concentrations outside of the cell, the concentration and voltage differences both drive them into the cell when na+ channels open. depolarization opens both the sodium and potassium channels in the membrane, allowing the ions to flow into and out of the axon, respectively. if the depolarization is small (say, increasing vm from −70 mv to −60 mv), the outward potassium current overwhelms the inward sodium current and the membrane repolarizes back to its normal resting potential around −70 mv. however, if the depolarization is large enough, the inward sodium current increases more than the outward potassium current and a runaway condition (positive feedback) results: the more inward current there is, the more vm increases, which in turn further increases the inward current. a sufficiently strong depolarization (increase in vm) causes the voltage-sensitive sodium channels to open; the increasing permeability to sodium drives vm closer to the sodium equilibrium voltage ena≈ +55 mv. the increasing voltage in turn causes even more sodium channels to open, which pushes vm still further towards ena. this positive feedback continues until the sodium channels are fully open and vm is close to ena. the sharp rise in vm and sodium permeability correspond to the rising phase of the action potential. the critical threshold voltage for this runaway condition is usually around −45 mv, but it depends on the recent activity of the axon. a cell that has just fired an action potential cannot fire another one immediately, since the na+ channels have not recovered from the inactivated state. the period during which no new action potential can be fired is called the absolute refractory period. at longer times, after some but not all of the ion channels have recovered, the axon can be stimulated to produce another action potential, but with a higher threshold, requiring a much stronger depolarization, e.g., to −30 mv. the period during which action potentials are unusually difficult to evoke is called the relative refractory period. peak phase the positive feedback of the rising phase slows and comes to a halt as the sodium ion channels become maximally open. at the peak of the action potential, the sodium permeability is maximized and the membrane voltage vm is nearly equal to the sodium equilibrium voltage ena. however, the same raised voltage that opened the sodium channels initially also slowly shuts them off, by closing their pores; the sodium channels become inactivated. this lowers the membrane's permeability to sodium relative to potassium, driving the membrane voltage back towards the resting value. at the same time, the raised voltage opens voltage-sensitive potassium channels; the increase in the membrane's potassium permeability drives vm towards ek. combined, these changes in sodium and potassium permeability cause vm to drop quickly, repolarizing the membrane and producing the "falling phase" of the action potential. afterhyperpolarization the depolarized voltage opens additional voltage-dependent potassium channels, and some of these do not close right away when the membrane returns to its normal resting voltage. in addition, further potassium channels open in response to the influx of calcium ions during the action potential. the intracellular concentration of potassium ions is transiently unusually low, making the membrane voltage vm even closer to the potassium equilibrium voltage ek. the membrane potential goes below the resting membrane potential. hence, there is an undershoot or hyperpolarization, termed an afterhyperpolarization, that persists until the membrane potassium permeability returns to its usual value, restoring the membrane potential to the resting state. refractory period each action potential is followed by a refractory period, which can be divided into an absolute refractory period, during which it is impossible to evoke another action potential, and then a relative refractory period, during which a stronger-than-usual stimulus is required. these two refractory periods are caused by changes in the state of sodium and potassium channel molecules. when closing after an action potential, sodium channels enter an "inactivated" state, in which they cannot be made to open regardless of the membrane potential—this gives rise to the absolute refractory period. even after a sufficient number of sodium channels have transitioned back to their resting state, it frequently happens that a fraction of potassium channels remains open, making it difficult for the membrane potential to depolarize, and thereby giving rise to the relative refractory period. because the density and subtypes of potassium channels may differ greatly between different types of neurons, the duration of the relative refractory period is highly variable. the absolute refractory period is largely responsible for the unidirectional propagation of action potentials along axons. at any given moment, the patch of axon behind the actively spiking part is refractory, but the patch in front, not having been activated recently, is capable of being stimulated by the depolarization from the action potential. propagation main article: nerve conduction velocity the action potential generated at the axon hillock propagates as a wave along the axon. the currents