<P> 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 . 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 . </P> <P> 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 . </P> <P> 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 . </P> <P> 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 V . This changes the membrane's permeability to those ions . Second, according to the Goldman equation, this change in permeability changes in the equilibrium potential E, and, thus, the membrane voltage V. 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 V in opposite ways, or at different rates . For example, although raising V opens most gates in the voltage - sensitive sodium channel, it also closes the channel's "inactivation gate", albeit more slowly . Hence, when V is raised suddenly, the sodium channels open initially, but then close due to the slower inactivation . </P>

The rising phase of the action potential is due to