Action Potential Waveform and Refractoriness

Phases of the Action Potential Introduction An action potential is a rapid, temporary change in the electrical potential across the neuronal membrane. It occurs in distinct phases that reflect the opening and closing of voltage-gated sodium and potassium channels. Understanding these phases is essential because they explain how neurons generate and transmit electrical signals. Each phase has a specific cause at the molecular level, and together they create the characteristic "spike" waveform that you see in recordings of neuronal activity. The key insight is that the phases depend on how the permeability (or conductance) of the membrane to sodium and potassium ions changes over time. By tracking which ions are flowing and in which direction, you can understand what happens at each stage. Rising Phase (Depolarization) The rising phase begins when a stimulus depolarizes the neuron's membrane enough to reach threshold—typically around −55 mV. At this point, voltage-gated sodium channels suddenly open, flooding the membrane with a property called increased sodium permeability. Once sodium channels open, sodium ions rush into the cell because they are driven by two forces: the concentration gradient (more Na⁺ outside) and the electrical gradient (the inside is negative and attracts positive charges). This massive inward sodium current overwhelms the small outward potassium current that is always leaking out, so the membrane potential rapidly becomes more positive. Here's the critical part: as the membrane depolarizes, it opens even more sodium channels. This is a positive feedback loop. The more Na⁺ that enters, the more positive the membrane becomes, which opens more channels, allowing even more Na⁺ to enter. This positive feedback causes extremely rapid depolarization—on the order of milliseconds. The membrane voltage during this phase is driven toward the sodium equilibrium potential ($E{\text{Na}}$), which is approximately +55 mV. This is the theoretical voltage at which there would be no net flow of sodium across the membrane. However, the membrane never quite reaches this value because sodium channels begin to inactivate before equilibrium is reached. Key takeaway: Rising phase = Na⁺ channels open → rapid Na⁺ influx → positive feedback → fast depolarization. Peak Phase At the peak, the membrane potential reaches its maximum value, typically around +30 mV in neurons. This is lower than $E{\text{Na}}$ (+55 mV) because of what's happening simultaneously. At the peak, two crucial events occur almost at the same time: Sodium channels inactivate: The depolarization that opened the sodium channels now triggers their inactivation. The channels close and become temporarily unresponsive to voltage changes. This is a different state from the "closed" resting state—inactivated channels are "locked" shut. Potassium channels open: Voltage-gated potassium channels are sensitive to depolarization, but they respond more slowly than sodium channels. By the time the membrane reaches +30 mV, these K⁺ channels finally open. This increases the membrane's permeability to potassium, and K⁺ begins to flow out of the cell. The membrane potential at the peak represents a balance—still largely driven toward $E{\text{Na}}$ because sodium channels are maximally open, but increasingly influenced by the outward K⁺ current that is just beginning. Key takeaway: Peak = maximum voltage when Na⁺ channels inactivate and K⁺ channels open. Falling Phase (Repolarization) During the falling phase, the membrane potential rapidly returns toward the resting potential of approximately −70 mV. Two things happen to cause this: Sodium permeability decreases rapidly: The inactivated sodium channels stay closed, so almost no more Na⁺ can enter the cell. Potassium permeability remains high: The K⁺ channels that opened at the peak are still open, so K⁺ continues to flow out. With Na⁺ influx shut down and K⁺ efflux running strong, the membrane voltage is now driven toward the potassium equilibrium potential ($E{\text{K}}$), which is approximately −90 mV. The outward K⁺ current dominates, causing rapid repolarization. The falling phase is essentially the mirror image of the rising phase: instead of positive feedback accelerating depolarization, you have unopposed outward current accelerating repolarization. Key takeaway: Falling phase = Na⁺ channels inactivate + K⁺ channels remain open → K⁺ flows out → rapid repolarization. Afterhyperpolarization (Undershoot) Here's where many students get confused: the membrane potential doesn't simply return to resting level and stop. Instead, it briefly becomes more negative than the resting potential, typically reaching about −80 to −90 mV before returning to baseline. This is called afterhyperpolarization (AHP) or undershoot. Why does this happen? The answer is that potassium channels stay open too long. These channels don't close the instant the membrane returns to resting potential. Instead, they remain open for a brief period, allowing K⁺ to continue flowing out of the cell. This continued outward current drives the voltage below resting level. Additionally, some K⁺ channels open specifically in response to calcium influx that occurred during the rising phase. Calcium enters through channels alongside the sodium, and calcium-activated K⁺ channels provide extra outward current. The membrane potential only returns to the true resting level once these K⁺ channels finally close and potassium permeability returns to its baseline value. Key takeaway: Afterhyperpolarization = K⁺ channels remain open after the membrane repolarizes, driving voltage below resting potential until K⁺ channels close. Refractory Periods The refractory periods are among the most important concepts in neurophysiology because they explain why action potentials travel in one direction and why neurons have a maximum firing frequency. Understanding refractory periods requires understanding the inactivation state of sodium channels. Absolute Refractory Period The absolute refractory period is the interval during which no new action potential can be generated, regardless of how strong the stimulus. This is a completely "refractory" state—the neuron is temporarily unexcitable. What's happening: During this period, sodium channels are in the inactivated state. Remember, inactivation is different from simply being closed. An inactivated channel has its inactivation gate physically blocking the pore, even though the activation gate is open. The channel is "locked" in this configuration. Because sodium channels are inactivated, no matter how much you depolarize the membrane, you cannot open these channels. You cannot generate an inward sodium current, so you cannot trigger a new action potential. When it occurs: The absolute refractory period begins when sodium channels start to inactivate (at the peak of the action potential) and ends when they return to the closed-but-non-inactivated state (during the falling phase or early afterhyperpolarization). Relative Refractory Period The relative refractory period comes immediately after the absolute refractory period. During this time, a new action potential can be generated, but only with a stronger-than-normal stimulus. What's happening: Sodium channels have finally returned to their closed, resting state and can open again. However, potassium channels remain open, creating a sustained outward current. Additionally, the membrane is hyperpolarized due to afterhyperpolarization, so it's more negative than normal. To reach threshold during the relative refractory period, you must overcome two obstacles: The outward K⁺ current pulling the voltage downward The hyperpolarized starting point (the membrane is at maybe −80 mV instead of the normal −70 mV) This means you need a stronger depolarizing stimulus than usual to reach threshold. The required stimulus might be, for example, the difference between −70 mV and −55 mV (15 mV of depolarization needed normally) versus −80 mV and −55 mV (25 mV of depolarization needed). When it occurs: The relative refractory period begins when sodium channels return to the resting state and lasts as long as potassium channels remain partially open and the membrane is hyperpolarized. Duration varies: Different neuron types have different potassium channel compositions, so the duration of the relative refractory period varies. Neurons with more or different types of K⁺ channels may have longer or shorter relative refractory periods. Functional Significance The refractory periods serve a crucial function: they ensure that action potentials propagate in only one direction along the axon. Here's how: When an action potential is generated at one location on an axon, it depolarizes the adjacent downstream region, triggering an action potential there. However, the region upstream (where the action potential just came from) is in its absolute refractory period. Even though the depolarization spreading backwards could theoretically trigger a new action potential, the sodium channels are inactivated, so a new action potential cannot form there. The signal therefore cannot "bounce back" and can only travel forward along the axon. Without absolute refractory periods, action potentials would fire bidirectionally, creating chaos in neural signaling. Summary of Channel States To fully master this topic, it helps to visualize the state of sodium and potassium channels at each phase: | Phase | Na⁺ Channels | K⁺ Channels | Result | |-------|--------------|------------|--------| | Resting | Closed | Closed (mostly) | Stable at −70 mV | | Rising | Opening → Maximally open | Closed | Rapid depolarization toward +30 mV | | Peak | Inactivating | Opening | Transition from Na⁺ to K⁺ dominance | | Falling | Inactivated | Open | Rapid repolarization toward −70 mV | | Afterhyperpolarization | Returning to closed | Still open | Hyperpolarization to −80 to −90 mV | | Absolute Refractory | Inactivated | Closing | Cannot fire a new action potential | | Relative Refractory | Closed (normal) | Partially open | Can fire with stronger stimulus |