Roles of Other Ions During Action Potential

The voltage-gated sodium channel is the main molecular switch responsible for rapid depolarization during an action potential. This channel protein features two separate gates: an activation gate near the outside of the cell and an inactivation gate near the inside. At a normal resting potential of -90{ mV}, the activation gate is closed, blocking sodium entry, while the inactivation gate remains open. When the membrane potential rises toward threshold, the electrical change causes the activation gate to flip open instantly, allowing a massive influx of sodium ions into the cell. Within fractions of a millisecond, the same voltage change causes the slower inactivation gate to swing shut, stopping sodium entry completely. This channel cannot open again until the membrane potential fully returns to its resting state.

Impermeable Negatively Charged Anions:

• Impermeable anions remain trapped inside the axon.
• Include intracellular proteins, organic phosphates, and sulfates.
• Cannot pass through membrane channels.
• Create internal negativity when a positive ions deficit exists.

Calcium Ions and Calcium Pumps:

• Calcium pumps transport Ca^{2+} from inside to outside.
• Maintains 10,000-fold calcium concentration gradient.
• Intracellular Ca^{2+} concentration is 10^{-7}\{ M}.
• Extracellular Ca^{2+} concentration is 10^{-3}{ M}.

Voltage-Gated Calcium Channels:

• Permeability of calcium is 1000-fold greater than sodium.
• Depolarization opens channels, causing calcium influx.
• Gating is slow, taking 10 to 20 times longer than sodium.
• Known as slow channels compared to fast sodium channels.
• Provide sustained depolarization in target cells.
• Abundant in cardiac muscle and smooth muscle.
• Drive smooth muscle action potentials lacking fast sodium channels.

Effect of Calcium Deficit on Sodium Channels:

• Extracellular Ca^{2+} binds exterior surfaces of sodium channels.
• Calcium positive charges alter sodium channel electrical state.
• Low Ca^{2+} activates sodium channels at lower voltages.
• Lowers threshold, making nerve fibers highly excitable.
• A 50\% Ca^{2+} drop causes spontaneous nerve discharge.
• Causes muscle tetany, potentially lethal via respiratory muscles.

 Initiation of the Action Potential

Positive-Feedback Cycle:

• Undisturbed nerve membrane maintains resting potential.
• Initial voltage rise opens voltage-gated sodium channels.
• Inflowing sodium increases voltage, opening more channels.
• Positive-feedback cycle activates all voltage-gated sodium channels.
• Rising potential subsequently closes sodium and opens potassium channels.

Threshold for Stimulation:

• Requires sodium influx to exceed potassium efflux.
• Requires sudden voltage rise of 15\{ mV} to 30\{ mV}.
• Shift from -90\{ mV} to -65\{ mV} initiates action potential.
• -65\{ mV} level is the threshold for stimulation.

Propagation of the Action Potential

Mechanism of Spread

• Action potential excites adjacent resting membrane areas.
• Local current circuits flow between depolarized and resting areas.
• Inward sodium ions carry positive charges along the axon core.
• Increases voltage 1\{ to }3\{ mm} inside myelinated fibers.
• Reaches threshold voltage, opening adjacent sodium channels.
• The depolarization process travels along the entire fiber length.
• Impulse refers to signal transmission along nerve/muscle fibers.

Direction of Propagation:

• Excitable membranes have no single propagation direction.
• Action potential travels in all directions away from stimulus.
• Spreads along all branches until the entire membrane depolarizes.

All-or-Nothing Principle:

• Depolarization travels over the entire membrane or not at all.
• Propagation stops if generated voltage falls below threshold.
• Continued propagation requires action potential-to-threshold ratio above 1.
• Ratio greater than 1 requirement is called safety factor.

Re-establishing Ionic Gradients

Need for Recharging

• Action potentials slightly reduce internal/external ion gradients.
• Single action potentials produce minute concentration changes.
• 100,000 to 50 million impulses occur before conduction ceases.
• Active metabolism restores original ionic gradients over time.

Role of Sodium-Potassium Pump:

•  The pump restores original sodium and potassium levels.
• Requires energy derived from the cell ATP system.
• Active pumping produces excess metabolic heat.
• Pumping activity increases with higher intracellular sodium concentration.
• Activity increases proportional to the third power of internal sodium.
• Doubling internal sodium increases pump activity eightfold.

Plateau in Some Action Potentials

Basic Characteristics

• Membrane potential remains near the peak for many milliseconds.
• Prolongs total duration of cell depolarization.
• Occurs in heart muscle fibers for 0.2\{ to }0.3\{ seconds}.
• Prolonged plateau causes sustained heart muscle contraction.

Causes of the Plateau:

• Fast voltage-gated sodium channels cause an initial spike.
• Slow voltage-gated calcium-sodium channels maintain plateau.
• Inward calcium flow keeps membrane potential elevated.
• Delayed opening of voltage-gated potassium channels delays repolarization.