Neurology | Resting Membrane, Graded, Action Potentials

The video introduces the core principles behind neuron excitability, outlining resting membrane potentials, graded potentials, and action potentials. It explains that resting membrane potentials define the baseline electrical charge of a neuron, while graded and action potentials represent dynamic changes essential for neural signaling. The discussion highlights how these electrical behaviors enable neurons to encode and transmit information.

Resting Membrane Potential: Voltage at Rest The resting membrane potential is defined as the voltage difference across a cell membrane when the cell is inactive, a state common to all cells but particularly vital in neurons. It typically ranges from -70 to -90 millivolts, with many texts favoring -70 mV as the standard value. Detailed examination reveals that careful cellular zooming shows ion movements across structures like the axon, cell body, and axon terminal, underscoring the foundation of neural electrical behavior.

Sodium-Potassium ATPases: Establishing Negative Charge The sodium-potassium ATPases actively pump three sodium ions out and two potassium ions into the cell, creating a net export of positive charge that shifts the internal voltage slightly negative. This process, even if only moving from an imagined starting point of zero to a small negative value, is essential for the development of the resting potential. Moreover, these pumps establish distinct ion concentration gradients, ensuring higher sodium outside and higher potassium inside, setting the stage for further neuronal electrical activity.

Potassium Efflux Drives Membrane Hyperpolarization Leaky potassium channels remain open, allowing potassium ions to exit the cell passively along their concentration gradient. The loss of potassium leaves behind immobile negatively charged anions, shifting the cell’s interior to a more negative voltage – potentially down to -90 millivolts. This mechanism is fundamental in establishing the neuron's resting membrane potential.

Sodium Influx and Differential Ion Permeability Maintain Resting Potential Leaky sodium channels enable sodium ions to enter the cell down their concentration gradient, although their impact is limited by the cell's much higher permeability to potassium. The modest sodium influx slightly counteracts the negative charge from potassium efflux, stabilizing the membrane potential around -70 millivolts. Together with the sodium-potassium pump, this balance of ion movements is critical for preparing the neuron for electrical signaling.

Potassium Equilibrium: Balancing Diffusion and Electric Forces Potassium ions exit the cell along their concentration gradient, which makes the cell’s interior negative and generates an opposing electrostatic force. Equilibrium is achieved when the outward diffusion is exactly counterbalanced by the inward pull of the negative charge. The Nernst equation uses a constant divided by the ion’s charge and the logarithm of the concentration ratio to determine an approximate equilibrium potential of -90 millivolts for potassium.

Sodium Contribution and Permeability-Driven Resting Potential Sodium equilibrium, calculated by the same principle, results in a potential of about +70 millivolts using its extracellular and intracellular concentrations. The overall resting membrane potential is determined by the weighted contributions of both ions, where potassium’s higher permeability exerts a dominant effect. This selective permeability ensures that the resting potential aligns closer to potassium’s equilibrium value, typically near -70 millivolts.

Modulating the Membrane: From Rest to Threshold Neurons maintain a resting membrane potential of about -70 mV that must shift toward a threshold near -55 mV to initiate an action potential. Graded potentials provide these subtle adjustments by either depolarizing the cell or, alternatively, hyperpolarizing it to a more negative value. These fine changes set the stage for whether the neuron will be activated.

Balancing Forces: Excitatory and Inhibitory Influences A depolarization that moves the potential toward the threshold is classified as an excitatory postsynaptic potential, which facilitates neuronal firing. Inhibition occurs when the cell is hyperpolarized further, moving away from the threshold and decreasing excitability. This push and pull between excitation and inhibition precisely regulates neuronal responses.

Neurotransmitter Action: Ligand-Gated Ion Channel Dynamics Neurotransmitters modulate neuronal activity by binding to ligand-gated ion channels that control ion flow. Glutamate, upon binding, opens channels that allow cations like sodium and calcium to enter, depolarizing the neuron. Conversely, GABA activates channels for chloride entry or potassium exit, hyperpolarizing the cell and reducing its likelihood to fire.

A neuron’s membrane potential is shaped by the continuous contest between excitatory and inhibitory inputs. Starting from a resting state of -70 mV, the neuron must reach a threshold of -55 mV to open voltage-gated sodium channels and trigger an action potential. Multiple excitatory signals can summate over time to counteract inhibitory influences, ultimately pushing the membrane potential to the critical threshold. The ability to accumulate more excitatory than inhibitory inputs is essential for the all-or-none firing response.

A single presynaptic neuron can build up successive excitatory postsynaptic potentials over time, gradually moving the postsynaptic neuron's membrane potential from a resting state to the threshold needed for an action potential; this process is known as temporal summation. Multiple presynaptic neurons firing simultaneously contribute their EPSPs at once, and their combined effect, termed spatial summation, pushes the postsynaptic neuron to the threshold as well. Both strategies require an accumulation of excitatory inputs that outweigh inhibitory signals, ensuring that the depolarization reaches the critical level for triggering neuronal firing.

Reaching the Threshold for Neural Activation The neuron begins at a resting potential of -70 mV where graded potentials accumulate. Summated excitatory postsynaptic inputs push the membrane potential to a critical threshold of -55 mV. At this precise voltage, highly sensitive channels in the trigger zone are primed for activation.

Sodium Influx Drives Rapid Depolarization Once the threshold is reached, voltage-gated sodium channels at the axon hillock open, allowing a powerful influx of sodium ions. This influx rapidly shifts the membrane potential from -55 mV to +30 mV, flipping the electrical polarity. The activation and subsequent closure of specific sodium channel gates ensure the unidirectional propagation of the depolarizing wave along the axon.

Calcium Entry and Neurotransmitter Release The depolarizing wave reaching the axon terminal triggers the opening of voltage-gated calcium channels at +30 mV. The resulting calcium influx prompts vesicle fusion with the terminal membrane by linking key protein complexes. This process leads to the exocytosis of neurotransmitters into the synaptic cleft, facilitating communication with the next cell.

Defining Neuronal Voltage Shifts Neuronal depolarization converts a negative interior into a more positive state, setting the stage for an active signal. Repolarization returns the membrane potential to its resting negative level, while hyperpolarization drives it even further negative. These voltage changes precisely regulate the opening and closing of ion channels.

Resetting Membrane Potential via Ion Flow After a depolarization peak at +30 mV, voltage-gated potassium channels open and allow potassium ions to exit, shifting the voltage toward -90 mV. This ion efflux not only repolarizes the cell but also inhibits voltage-gated calcium channels, preventing further neurotransmitter release. The combined action of ion pumps and leak channels eventually restores the resting membrane potential.

From Resting Potential to Threshold via Summation A graph illustrates time on the x-axis and voltage on the y-axis, starting at a resting membrane potential of -70 mV maintained by sodium–potassium ATPases and leaky ion channels. Electrical inputs, embodied as EPSPs, progressively sum and overcome IPSPs to drive the membrane toward a threshold of approximately -55 mV. This careful balance of ion permeability sets the stage for the opening of voltage‐gated sodium channels as the cell becomes increasingly depolarized.

Sodium Channel Dynamics and Potassium-Mediated Repolarization Voltage-gated sodium channels, featuring an external activation gate and an internal inactivation gate, are configured with closed activation and open inactivation gates at rest. Once threshold is reached, the activation gate opens and the inactivation gate begins to close, enabling an influx of sodium that drives depolarization toward a peak of +30 mV, where the inactivation gate finally seals the channel. At this peak, voltage-gated potassium channels open more slowly, allowing potassium to leak out, which repolarizes and briefly hyperpolarizes the membrane before returning to equilibrium.

Absolute Refractory Period Locks the Channel When the cell reaches its peak potential, the voltage-gated sodium channels become locked in an inactivated state, preventing any further stimulation until a return to the resting membrane potential occurs. The inactivation gates remain closed while the activation gates are reset, making it impossible to trigger another action potential regardless of additional voltage. This absolute refractory phase ensures that the membrane remains unresponsive until it has fully reset.

Relative Refractory Period Requires Extra Voltage Once the cell has returned to the resting state, it typically finds itself hyperpolarized at around -90 mV, which is below the standard threshold of -55 mV. This hyperpolarization means that additional, stronger stimulation is needed to bring the cell from this lower potential back up to the threshold level. In this period, known as the relative refractory phase, a heightened voltage is required to re-open the sodium channels and initiate another action potential.