Key aspects of studying physiology
Unlike anatomy and histology, physiology is a process-oriented discipline. While anatomy describes structures (what is visible is what is named), physiology studies dynamics: the initial state, the final state, and the transition mechanism between them. A similar approach is applied in biochemistry, pharmacology, pathophysiology, and clinical disciplines.
Methodologically, it is advisable to study such subjects "from the end"—by understanding the biological meaning of the process. The action potential underlies the perception of touch, hearing (hair cells of the cochlea), cardiac activity, nerve impulse propagation, and many other body functions.
Resting membrane potential
At rest, the cell membrane is polarized: the inner surface is negatively charged, and the outer surface is positively charged. For neurons, the magnitude of the resting membrane potential is about −70 mV. The establishment of this charge is maintained by several ion mechanisms:
- Potassium leak channels — constantly open, providing passive efflux of K⁺ out of the cell down its concentration gradient. Since potassium is positively charged, its efflux makes the inner side of the membrane more negative.
- The escaped potassium ions accumulate near the outer surface of the membrane, forming a "potassium cap" that electrostatically repels other cations (e.g., Ca²⁺).
- Na⁺/K⁺-ATPase — an active transporter that utilizes the energy of ATP (adenosine triphosphate). During one cycle, it pumps out 3 Na⁺ ions and pumps in 2 K⁺ ions, maintaining concentration gradients and further contributing to the formation of the intracellular negative charge.
Action potential: phases and mechanisms
The cell is constantly exposed to various stimuli. Subthreshold stimuli do not cause excitation, whereas a threshold stimulus shifts the membrane potential to the critical level of depolarization (approximately −50 to −45 mV). From this point on, an action potential develops.
- Depolarization. Voltage-gated sodium channels open. Na⁺ ions rush into the cell down their electrochemical gradient in an avalanche-like manner, and the membrane charge rapidly changes from negative to positive, reaching approximately +35 mV.
- Overshoot (spike). The peak portion of the curve where the membrane inverts its polarity. Sodium channels have inactivation gates that close upon reaching the maximum, halting the influx of Na⁺.
- Repolarization. Voltage-gated potassium channels open, K⁺ rapidly exits the cell, and the membrane charge returns to negative values.
- After-potentials. Following repolarization, minor deviations may occur: a negative after-potential (hyperpolarization) and a positive after-potential, caused by the inertia of ionic currents and the activity of Na⁺/K⁺-ATPase, which restores initial ion concentrations.
A distinction is made between rapid and slow depolarization, as well as rapid and slow repolarization, depending on the rate of membrane potential change at different segments of the curve.
Tissue excitability and refractory periods
Concurrently with the action potential, tissue excitability—its ability to respond to a new stimulus—changes.
- During the slow depolarization phase (up to the critical level), excitability is increased: the cell is closer to the threshold.
- During the rapid depolarization phase and the peak, absolute refractoriness occurs: sodium channels are inactivated, and no stimulus, regardless of its strength, is capable of generating a new action potential.
- During the repolarization phase, relative refractoriness is established: some channels have recovered, and a strong suprathreshold stimulus can elicit a response.
- During the after-potential period, excitability fluctuates: phases of supernormal and subnormal excitability are possible, after which the tissue returns to its baseline level.
Key concepts and terminology
To correctly describe bioelectrical phenomena in physiology, established terminology is used:
- Polarization — the presence of a potential difference between the sides of the membrane.
- Depolarization — a decrease in the negative charge of the inner side of the membrane up to sign inversion.
- Repolarization — restoration of the original negative charge.
- Hyperpolarization — an increase in the negative charge beyond the resting level.
- Spike (overshoot) — the peak phase with a positive value of the membrane potential.
- Refractoriness — a decrease or complete absence of excitability during and after an action potential.
Key points
- The resting membrane potential of a neuron is about −70 mV and is established by potassium leak channels and the activity of Na⁺/K⁺-ATPase.
- The Na⁺/K⁺-ATPase pumps 3 Na⁺ out and 2 K⁺ in, using ATP energy.
- An action potential is triggered when the critical level of depolarization is reached (about −50 mV).
- Depolarization is driven by Na⁺ influx through voltage-gated sodium channels, while repolarization is driven by K⁺ efflux through voltage-gated potassium channels.
- The action potential peak (overshoot) reaches approximately +35 mV.
- After-potentials reflect the restoration of ion gradients following the spike.
- Absolute and relative refractory periods are distinguished during an action potential.
- The action potential is the basis for the function of neurons, muscles, the heart, and sensory systems.