Neurons communicate through electrical signals, with the membrane potential playing a crucial role. This potential difference between the inside and outside of a neuron is maintained by ion concentrations and selective permeability of the cell membrane.

Action potentials are rapid, all-or-nothing events that allow neurons to transmit information over long distances. These electrical signals are generated by the coordinated opening and closing of voltage-gated ion channels, primarily sodium and potassium channels.

Resting Membrane Potential

Ionic Basis of Resting Membrane Potential

• The resting membrane potential is the difference in electrical charge between the inside and outside of a neuron, typically around -70mV, with the inside being more negative relative to the outside
• Primarily determined by the concentration gradients of potassium (K+) and sodium (Na+) ions across the cell membrane
  • K+ is more concentrated inside the cell
  • Na+ is more concentrated outside the cell
• The cell membrane is selectively permeable, allowing K+ to diffuse out of the cell more easily than Na+ can diffuse into the cell, resulting in a net negative charge inside the cell
• The sodium-potassium pump (Na+/K+-ATPase) actively transports Na+ out of the cell and K+ into the cell, maintaining the concentration gradients and contributing to the resting membrane potential
• Chloride (Cl-) ions also play a role in maintaining the resting membrane potential, with their distribution across the cell membrane being determined by the chloride equilibrium potential

Factors Influencing Resting Membrane Potential

• The permeability of the cell membrane to different ions, which is determined by the presence and activity of ion channels (leak channels)
• The activity of the sodium-potassium pump, which maintains the concentration gradients of Na+ and K+ across the cell membrane
• The presence of other ions, such as calcium (Ca2+) and magnesium (Mg2+), which can influence the membrane potential through their own concentration gradients and ion channels
• The Nernst equation describes the equilibrium potential for a specific ion based on its concentration gradient across the membrane
  • $E_{ion} = \frac{RT}{zF} \ln \frac{[ion]_{outside}}{[ion]_{inside}}$
• The Goldman-Hodgkin-Katz equation describes the resting membrane potential taking into account the permeability and concentration gradients of multiple ions
  • $V_m = \frac{RT}{F} \ln \frac{P_K[K^+]_{outside} + P_{Na}[Na^+]_{outside} + P_{Cl}[Cl^-]_{inside}}{P_K[K^+]_{inside} + P_{Na}[Na^+]_{inside} + P_{Cl}[Cl^-]_{outside}}$

Action Potential Generation and Propagation

Generation of Action Potentials

• Action potentials are rapid, transient changes in the membrane potential that occur when a neuron is sufficiently stimulated, typically by synaptic input or sensory stimuli
• The generation of an action potential begins with the opening of voltage-gated sodium channels when the membrane potential reaches a threshold value (around -55mV), allowing Na+ to rapidly enter the cell and depolarize the membrane
• As the membrane potential becomes more positive, more voltage-gated sodium channels open, leading to a positive feedback loop and the rapid depolarization phase of the action potential
• The rising phase of the action potential is followed by a falling phase, during which voltage-gated potassium channels open, allowing K+ to exit the cell and repolarize the membrane back towards the resting potential
• After the action potential, there is a brief refractory period during which the neuron cannot generate another action potential, due to the inactivation of sodium channels and the continued efflux of K+

Propagation of Action Potentials

• Action potentials propagate along the axon in a self-regenerating manner, with the depolarization of one segment of the axon triggering the opening of voltage-gated sodium channels in the adjacent segment, leading to a wave of depolarization traveling along the axon
• The speed of action potential propagation is increased by the presence of myelin sheaths around the axon, which insulate the axon and allow the action potential to jump between gaps in the myelin (nodes of Ranvier), a process called saltatory conduction
• The direction of action potential propagation is determined by the refractory period, as the recently activated segment of the axon cannot generate another action potential, ensuring the signal travels in one direction
• The diameter of the axon also influences the speed of action potential propagation, with larger diameter axons conducting action potentials more rapidly than smaller diameter axons
• Factors that can affect action potential propagation include axonal damage, demyelination (multiple sclerosis), and changes in ion channel function or expression

Graded vs Action Potentials

Characteristics of Graded Potentials

• Graded potentials are small, localized changes in the membrane potential that vary in amplitude depending on the strength of the stimulus
• Can be either depolarizing (excitatory) or hyperpolarizing (inhibitory)
• Decay over short distances and do not propagate far from their site of origin
• Typically generated by synaptic input or sensory stimuli and can summate to trigger an action potential if the membrane potential reaches the threshold value
• Examples of graded potentials include:
  • Receptor potentials in sensory neurons
  • Synaptic potentials (excitatory and inhibitory postsynaptic potentials) in postsynaptic neurons
  • Electrotonic potentials in dendrites and cell bodies

Characteristics of Action Potentials

• Action potentials are all-or-none events with a fixed amplitude
• Always involve depolarization followed by repolarization
• Can propagate over long distances along the axon without decaying
• Generated when the membrane potential reaches a threshold value, typically due to the summation of graded potentials
• Exhibit a refractory period during which another action potential cannot be generated
• Examples of action potentials include:
  • Spikes in neurons
  • Muscle fiber contraction in skeletal muscle cells
  • Cardiac action potentials in heart muscle cells

Voltage-Gated Channels in Action Potentials

Role of Voltage-Gated Sodium Channels

• Voltage-gated sodium (Na+) channels are responsible for the rapid depolarization phase of the action potential, opening in response to membrane depolarization and allowing Na+ to enter the cell
• The opening and closing of voltage-gated sodium channels are regulated by changes in the membrane potential, with specific activation and inactivation thresholds
• The inactivation of voltage-gated sodium channels during the falling phase of the action potential contributes to the refractory period, during which the neuron cannot generate another action potential
• Mutations or dysfunctions in voltage-gated sodium channels can lead to various neurological disorders (epilepsy, certain types of paralysis)

Role of Voltage-Gated Potassium Channels

• Voltage-gated potassium (K+) channels are responsible for the repolarization phase of the action potential, opening in response to membrane depolarization and allowing K+ to exit the cell
• The delayed opening of voltage-gated potassium channels compared to sodium channels allows for the rapid depolarization and the subsequent repolarization of the membrane
• The activity of voltage-gated potassium channels contributes to the afterhyperpolarization, which helps to prevent the neuron from generating another action potential during the refractory period
• Different subtypes of voltage-gated potassium channels (A-type, delayed rectifier) have varying activation and inactivation kinetics, shaping the duration and frequency of action potentials
• Mutations or dysfunctions in voltage-gated potassium channels can lead to neurological disorders (ataxia, epilepsy) and cardiac arrhythmias (long QT syndrome)